Page last updated: 2024-11-05

cysteamine

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Description

Cysteamine: A mercaptoethylamine compound that is endogenously derived from the COENZYME A degradative pathway. The fact that cysteamine is readily transported into LYSOSOMES where it reacts with CYSTINE to form cysteine-cysteamine disulfide and CYSTEINE has led to its use in CYSTINE DEPLETING AGENTS for the treatment of CYSTINOSIS. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

cysteamine : An amine that consists of an ethane skeleton substituted with a thiol group at C-1 and an amino group at C-2. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID6058
CHEMBL ID602
CHEBI ID17141
MeSH IDM0005535

Synonyms (153)

Synonym
2 aminoethanethiol
beta mercaptoethylamine
beta-aminoethylthiol
mercaptaminum
beta-mea
mercaptamina
2-amino-ethanethiol
CHEBI:17141 ,
2-amino-1-ethanethiol
DIVK1C_006750
NCI60_002000
nsc-647528
D03634
cysteamine (usan)
mercaptamine (inn)
wr 347
cisteamina [italian]
lambraten
cysteamine [usan:ban]
l 1573
nsc 647528
cysteamin
cystagon
mercamine
mercaptaminum [inn-latin]
1-amino-2-mercaptoethylamine
decarboxycysteine
2-mercaptoethanamine
lambratene
mercaptoethylamine
riacon
(2-mercaptoethyl)amine
hsdb 7353
mea (mercaptan)
ethanethiol, 2-amino-
ccris 3083
l-1573 ,
cysteinamine
mercaptamina [inn-spanish]
einecs 200-463-0
SPECTRUM_001755
bdbm7968
2-aminoethane-1-thiol
NCGC00015691-01
lopac-m-6500
becaptan
.beta.-mercaptoethylamine
2-aminoethyl mercaptan
nsc647528
STK315355
beta-mercaptoethylamine
2-aminoethanethiol
60-23-1
mercaptamine
thioethanolamine
C01678
beta-aminoethanethiol
cysteamine
DB00847
KBIO1_001694
KBIOSS_002235
KBIO2_002235
KBIO2_004803
KBIO2_007371
SPECPLUS_000654
NCGC00162236-01
cysteamine, free base
C-9500 ,
cysteamine, ~95%
cysteamine, >=98.0% (rt)
2DFDA1F8-7010-4225-8280-AB1C4C43F546
A0648
NCGC00015691-04
mercaptamin
ethanethiolamine
2-mercaptoethylamine
cysteamide
cisteamina
BMSE000388
cysteamine bitartate
aminoethyl mercaptan
CHEMBL602
A832648
AKOS003793343
NCGC00162236-02
DHL ,
cysteamine [usan]
5ux2sd1ke2 ,
mercaptamine [inn]
cystaran
unii-5ux2sd1ke2
tox21_113092
dtxcid902875
dtxsid3022875 ,
cas-60-23-1
CCG-204834
NCGC00015691-03
NCGC00015691-02
|a-mercaptoethylamine
mecramine
merkamin
mercamin
FT-0611243
cysteamine [mi]
cysteamine [vandf]
mercaptamine [who-dd]
cysteamine [hsdb]
mercaptamine [mart.]
cysteamine [inci]
S6402
gtpl7440
HY-77591A
BP-13401
mercapto ethylamine
2-amino-ethyl thiol
.beta.-aminoethylthiol
.beta.-aminoethanethiol
.beta.-mea
cystagone
AB00053754_09
AB00053754_10
F0001-1576
b-mercaptoethylamine
b-mea
mfcd00008196
cash
b-aminoethylthiol
b-aminoethanethiol
|a-mea
SBI-0050727.P003
2,3-deshydrolanthionine
Q617563
BCP15015
AMY202100105
SDCCGSBI-0050727.P004
NCGC00015691-14
2-aminoethanethiol;cysteamine, beta-mercaptoethylamine, 2-mercaptoethylamine, decarboxycysteine, thioethanolamine, mercaptamine
beta-mercaptoethylamine;2-aminoethanethiol;2-mercaptoethylamine
D88299
D88360
2-aminoethane-1-thiol; cysteamine
AS-56218
-mercaptoethylamine;2-aminoethanethiol;2-mercaptoethylamine
SB75360
oxu ,
2-aminoethylthiol
1-amino-2-mercaptoethane
s01xa21
mercaptamina (inn-spanish)
mercaptaminum (inn-latin)
mercaptamine (mart.)
a16aa04
EN300-33931

Research Excerpts

Overview

Cysteamine (CA) is a cystine depleting agent used in the treatment of cystinosis and many other diseases. Cysteamine is an aminothiol naturally present in cells of the human body as an antioxidant resulting from the degradation of Coenzyme A.

ExcerptReferenceRelevance
"Cysteamine (CA) is a cystine depleting agent used in the treatment of cystinosis and many other diseases. "( Lab-on-a-disc for ultrafast plasmonic assay of cysteamine.
Cho, YK; Karmacharya, M; Kumar, S; Lee, C, 2021
)
2.32
"Cysteamine is an aminothiol naturally present in cells of the human body as an antioxidant resulting from the degradation of Coenzyme A. "( Topical Stabilized Cysteamine as a New Treatment for Hyperpigmentation Disorders: Melasma, Post-Inflammatory Hyperpigmentation, and Lentigines.
Desai, S; Grimes, P; Hartman, C; Shah, S, 2021
)
2.39
"Cysteamine was confirmed to be an effective treatment for melasma, with equivalent results to HC in reducing mMASI score and improving quality of life, despite lesser melanin index reduction observed. "( Comparison of the efficacy of cysteamine 5% cream and hydroquinone 4%/ascorbic acid 3% combination cream in the treatment of epidermal melasma.
Bagheri, Z; Karimi, F; Kasraee, B; Sepaskhah, M, 2022
)
2.45
"Cysteamine is a very well-tolerated US FDA-approved drug used chronically as a topical ophthalmic solution to treat ocular cystinosis in patients who receive it hourly or QID lifelong at concentrations 6 times higher than that required to inhibit SARS CoV-2 in tissue culture."( In vitro activity of cysteamine against SARS-CoV-2 variants.
Ferrari, MG; Gavin, RF; Navarrete, J; Pal, R; Thoene, J; Towne, A; Wattay, L,
)
1.17
"Cysteamine is a small aminothiol endogenously derived from coenzyme A degradation. "( Cysteamine revisited: repair of arginine to cysteine mutations.
Ben-Omran, T; Blom, HJ; Dewik, AN; Gallego-Villar, L; Häberle, J; Hannibal, L; Kruger, WD; Nasrallah, GK; Thöny, B, 2017
)
3.34
"Cysteamine is a TG2 inhibitor and proteostasis regulator with the potential to restore autophagy."( Cysteamine-mediated clearance of antibiotic-resistant pathogens in human cystic fibrosis macrophages.
Albastroiu, F; Amer, AO; Assani, KD; Kopp, BT; Rinehardt, H; Schlesinger, LS; Shell, R; Shrestha, CL; Zhang, S, 2017
)
2.62
"Cysteamine is an endogenous aminothiol produced in mammalian cells as a consequence of coenzyme A metabolism through the activity of the vanin family of pantetheinase ectoenzymes. "( Cysteamine, an Endogenous Aminothiol, and Cystamine, the Disulfide Product of Oxidation, Increase Pseudomonas aeruginosa Sensitivity to Reactive Oxygen and Nitrogen Species and Potentiate Therapeutic Antibiotics against Bacterial Infection.
Cole, M; Doumith, M; Fraser-Pitt, DJ; Hill, RLR; Hopkins, KL; Kowalczuk, A; Lovie, E; Mercer, DK; O'Neil, DA; Perenyi, P; Robertson, J; Smith, D; Woodford, N, 2018
)
3.37
"L-Cysteamine is a biological antioxidant produced during the coenzyme A metabolism cycle and is naturally present in all mammalian cells. "( Significant therapeutic response to cysteamine cream in a melasma patient resistant to Kligman's formula.
Farshi, S; Kasraee, B; Mansouri, P, 2019
)
1.51
"Cysteamine bitartrate is a US Food and Drug Administration-approved therapy for nephropathic cystinosis also postulated to enhance glutathione biosynthesis. "( Pre-clinical evaluation of cysteamine bitartrate as a therapeutic agent for mitochondrial respiratory chain disease.
Bennett, M; Falk, MJ; Guha, S; Konkwo, C; Kwon, YJ; Lavorato, M; Lightfoot, R; Mathew, ND; Nakamaru-Ogiso, E; Ostrovsky, J; Peng, M; Polyak, E; Seiler, C; Xiao, R; Zhang, Z, 2019
)
2.25
"Cysteamine is an amino thiol with the chemical formula HSCH2CH2NH2. "( Cysteamine: an old drug with new potential.
Besouw, M; Levtchenko, E; Masereeuw, R; van den Heuvel, L, 2013
)
3.28
"Cysteamine is a cheap and commercially available aminothiol and is also the most important chelating ligand in coordination chemistry possessing the ability to coordinate to Hg(2+) and melamine."( Colorimetric sensing strategy for mercury(II) and melamine utilizing cysteamine-modified gold nanoparticles.
Huang, H; Jiang, L; Ma, Y; Mei, Y; Song, R; Tian, D, 2013
)
1.35
"Cysteamine is an essential component of treatment."( N-acetyl-cysteine is associated to renal function improvement in patients with nephropathic cystinosis.
Aparecido Volpini, R; Cunha Sanches, TR; de Bragança, AC; Lopes Neri, LA; Macaferri da Fonseca, FA; Moreira Filho, CA; Pache de Faria Guimaraes, L; Seguro, AC; Shimizu, MH; Sumita, NM; Vaisbich, MH, 2014
)
1.12
"Cysteamine is a potential solution to these unmet medical needs and is described here for the first time as (Lynovex®) a single therapy with the potential to deliver mucoactive, antibiofilm and antibacterial properties; both in oral and inhaled delivery modes."( Cysteamine (Lynovex®), a novel mucoactive antimicrobial & antibiofilm agent for the treatment of cystic fibrosis.
Charrier, C; Fraser-Pitt, D; Kowalczuk, A; Mercer, D; O'Neil, D; Robertson, J; Rodger, C; Shand, N, 2014
)
2.57
"Cysteamine is a mucolytic agent used to reduce the viscosity of mucus through the disruption of proteins, which are also important components of the extracellular matrix of biofilms."( Cysteamine Enhances Biofilm Eradication Efficacy of Calcium Hydroxide.
Guo, W; Lim, KC; Quah, SY; Tan, KS; Yu, VS, 2016
)
2.6
"Cysteamine (Cys) is a small, naturally occurring amino-thiol that has very low toxicity in vivo and is approved for clinical use in the life-long treatment of the kidney disorder nephropathic cystinosis."( Cysteamine broadly improves the anti-plasmodial activity of artemisinins against murine blood stage and cerebral malaria.
De Spiegeleer, B; Fortin, A; Gauthier, S; Gros, P; Hawari, J; Moradin, N; Stevenson, MM; Tam, M; Torre, S; Vandercruyssen, K, 2016
)
2.6
"Cysteamine is a degradation product of the amino acid cysteine and a reduced form of cystamine. "( Effects of cysteamine on MPTP-induced dopaminergic neurodegeneration in mice.
Chan, P; Sun, L; Wang, C; Wu, Y; Xu, S; Zhou, M, 2010
)
2.19
"Cysteamine is a cytotoxic agent, acting through generation of reactive oxygen species (ROS) and may decrease defense activity of antioxidative enzymes against ROS and induce duodenal ulcer."( Effects of captopril on the cysteamine-induced duodenal ulcer in the rat.
Jouyban, A; Karimi, I; Saghaei, F; Samini, M, 2012
)
1.39
"Cysteamine demonstrated to be an excellent scavenger also of alkoxyl- and peroxyl- type radicals."( Ascorbate and Cu(II)-induced oxidative degradation of high-molar-mass hyaluronan. Pro- and antioxidative effects of some thiols.
Bauerova, K; Drafi, F; Hrabarova, E; Juranek, I; Nagy, M; Priesolova, E; Soltes, L; Valachova, K, 2010
)
1.08
"Cysteamine is a reducing aminothiol used for inducing duodenal ulcer through mechanisms of oxidative stress related to thiol-derived H(2)O(2) reaction. "( Attenuation of cysteamine-induced duodenal ulcer with Cochinchina momordica seed extract through inhibiting cytoplasmic phospholipase A2/5-lipoxygenase and activating γ-glutamylcysteine synthetase.
Choi, KS; Hahm, KB; Hong, H; Kim, EH; Kim, JH; Lee, JS; Ock, CY, 2012
)
2.17
"Cysteamine is a chemo-sensitization and radioprotection agent and its antitumor effects have been investigated in various tumor cell lines and chemical induced carcinogenesis."( Cysteamine suppresses invasion, metastasis and prolongs survival by inhibiting matrix metalloproteinases in a mouse model of human pancreatic cancer.
Fujisawa, T; Gahl, WA; Joshi, BH; Patel, PS; Puri, RK; Rubin, B; Suzuki, A, 2012
)
2.54
"Cysteamine is a natural product of cells and constitutes the terminal region of the CoA molecule."( Cysteamine-related agents could be potential antidepressants through increasing central BDNF levels.
Tsai, SJ, 2006
)
2.5
"Cysteamine is a natural product of mammalian cells and found to be useful pharmacological alternative."( Therapeutic possibilities of cysteamine in the treatment of schizophrenia.
Lee, C; Pae, CU; Paik, IH, 2007
)
1.35
"Cysteamine (CS) is a sulfhydryl reducing agent that is known as a depletory agent of somatostatin."( Enhancement of mucosal immune responses in chickens by oral administration of cysteamine.
Gong, X; Lian, G; Yang, Q, 2007
)
1.29
"Cysteamine, which is a known antioxidant and anti-inflammatory agent, is believed to be a key regulator of essential metabolic pathways in organisms. "( Effect of thiol-containing molecule cysteamine on the induction of inducible nitric oxide synthase in hepatocytes.
Ito, S; Kaibori, M; Kamiyama, Y; Matsui, K; Nishizawa, M; Okumura, T; Ozaki, T; Tanaka, H; Tokuhara, K,
)
1.85
"Cysteamine is a cystine-depleting drug used in the treatment of cystinosis, a metabolic disorder caused by deficiency of the lysosomal cystine carrier. "( Antioxidant effect of cysteamine in brain cortex of young rats.
Biasibetti, M; da Silva Melo, DA; de Souza Wyse, AT; Dutra-Filho, CS; Kessler, A; Wajner, M; Wannmacher, CM, 2008
)
2.1
"Cysteamine is a useful pharmacologic tool for local somatostatin depletion."( Depletion of striatal somatostatin by local cysteamine injection.
Beal, MF; Martin, JB, 1984
)
1.25
"Cysteamine is a potent duodenal ulcerogen in rats. "( Role of delayed gastric emptying in the pathogenesis of cysteamine-induced duodenal ulcer in the rat.
Christiansen, J; Jensen, KK; Kirkegaard, P; Olsen, PS; Poulsen, SS, 1982
)
1.95
"Cysteamine is a recently licensed orphan drug used to treat the inherited metabolic disease cystinosis. "( A cost-effectiveness analysis of the orphan drug cysteamine in the treatment of infantile cystinosis.
Kaplan, RM; Schneider, JA; Soohoo, N,
)
1.83
"Cysteamine is an excellent scavenger of .OH and HOCl; it also reacts with H2O2, but no reaction with O2.- could be measured within the limits of our assay techniques."( The antioxidant action of taurine, hypotaurine and their metabolic precursors.
Aruoma, OI; Butler, J; Halliwell, B; Hoey, BM, 1988
)
1

Effects

Cysteamine (CSH) has an inhibitory effect on the secretion of PRL, GH and TSH. It has a marked effect on gastric acid production and serum gastrin. Cysteamine has a biphasic effect in kindled rats.

Cysteamine has a marked effect on gastric acid production and serum gastrin, even at the dose used in children with nephropathic cystinosis. Cysteamine is potentially effective in numerous animal models of Huntington's disease.

ExcerptReferenceRelevance
"Cysteamine (CSH) has an inhibitory effect on the secretion of PRL, GH and TSH. "( Cysteamine acts immediately to inhibit prolactin release and induce cellular changes in estradiol-primed male rats.
Reifel, CW; Saunders, SL; Shin, SH, 1984
)
3.15
"Cysteamine has a marked effect on gastric acid production and serum gastrin, even at the dose used in children with nephropathic cystinosis."( The effects of cysteamine on the upper gastrointestinal tract of children with cystinosis.
Murphy, JL; Wenner, WJ, 1997
)
1.37
"Cysteamine has a marked influence on the activity of mainly aldolase F-1, 6-P and glucose-6-P dehydrogenase in red blood cells in vitro."( The influence of the known radioprotective compounds on the metabolism of human red blood cell. Part II. The influence of cysteamine on enzymic systems.
Chmiel, J; Kopczyński, Z; Rybczyńska, M, 1976
)
1.18
"Cysteamine has a biphasic effect in kindled rats. "( Induction and suppression of seizures by cysteamine in hippocampal kindled rats.
Cottrell, GA; Robertson, HA, 1986
)
1.98
"Cysteamine has been reported as a promising depigmenting agent for melasma treatment and following formulation enhancement, its use is being reported."( Is cysteamine use effective in the treatment of melasma? A systematic review and meta-analysis.
da Silva, ÍCV; de Albuquerque-Junior, RLC; Dos Santos-Neto, AG; Melo, CR; Santana, AAM, 2022
)
2.06
"Cysteamine has been demonstrated as potentially effective in numerous animal models of Huntington's disease."( A randomized, double-blind, placebo-controlled trial evaluating cysteamine in Huntington's disease.
Allain, P; Azulay, JP; Bachoud-Lévi, AC; Bonneau, D; Calvas, F; Charles, P; Durr, A; Goizet, C; Krystkowiak, P; Maison, P; Olivier, A; Prundean, A; Reynier, P; Saudou, F; Scherer, C; Simonin, C; Tranchant, C; Verny, C; von Studnitz, E; Youssov, K, 2017
)
2.14
"Cysteamine has been utilized in vitro and ex vivo in four different genetic disorders, and thus provides "proof of principle" that aminothiols can modify Cys residues."( Cysteamine revisited: repair of arginine to cysteine mutations.
Ben-Omran, T; Blom, HJ; Dewik, AN; Gallego-Villar, L; Häberle, J; Hannibal, L; Kruger, WD; Nasrallah, GK; Thöny, B, 2017
)
2.62
"Cysteamine has direct anti-bacterial growth killing and improves human CF macrophage autophagy resulting in increased macrophage-mediated bacterial clearance, decreased inflammation, and reduced constitutive ROS production."( Cysteamine-mediated clearance of antibiotic-resistant pathogens in human cystic fibrosis macrophages.
Albastroiu, F; Amer, AO; Assani, KD; Kopp, BT; Rinehardt, H; Schlesinger, LS; Shell, R; Shrestha, CL; Zhang, S, 2017
)
2.62
"Cysteamine has been suggested to activate BDNF secretion; however, cysteamine protection was not blocked by BDNF pathway antagonists."( Cysteamine Protects Neurons from Mutant Huntingtin Toxicity.
Akimov, S; Arbez, N; Eddings, C; Ren, M; Roby, E; Ross, CA; Wang, X, 2019
)
2.68
"Cysteamine has improved survival and prognosis in cystinosis. "( Cysteamine (Cystagon®) adherence in patients with cystinosis in Spain: successful in children and a challenge in adolescents and adults.
Ariceta, G; Bedoya, R; Bravo, J; Bueno, A; Camacho, JA; Cantarell, C; Crespo, J; Daza, A; García-Nieto, V; Gil Calvo, M; Jiménez Del Cerro, LA; Justa, ML; Lara, E; Llamas, F; Muñoz, MA; Oppenheimer, F; Romero, R; Sanahuja, MJ; Santos, F; Urisarri, A; Valenciano, B; Vara, J, 2015
)
3.3
"Cysteamine has recently been shown to have in vitro properties potentially therapeutically beneficial in cystic fibrosis (CF). "( Cysteamine as a Future Intervention in Cystic Fibrosis Against Current and Emerging Pathogens: A Patient-based ex vivo Study Confirming its Antimicrobial and Mucoactive Potential in Sputum.
Devereux, G; Devlin, E; Fraser-Pitt, D; Mercer, D; O'Neil, D; Robertson, J, 2015
)
3.3
"Cysteamine has been used for treating cystinosis for many years, and furthermore it has also been used as a therapeutic agent for different diseases including Huntington's disease, Parkinson's disease (PD), nonalcoholic fatty liver disease, malaria, cancer, and others. "( Inhibition of peripubertal sheep mammary gland development by cysteamine through reducing progesterone and growth factor production.
Chu, M; Cui, L; Feng, Y; Kou, X; Li, L; Liu, X; Min, L; Shen, W; Zhang, H; Zhang, P; Zhao, Y, 2017
)
2.14
"Cysteamine has been reported to modulate energy homeostasis and exert significant growth-promoting effects in broiler chickens. "( Leptin is involved in the effects of cysteamine on egg laying of hens, characteristics of eggs, and posthatch growth of broiler offspring.
Dai, J; Hu, Y; Ni, Y; Ren, L; Zhao, R, 2008
)
2.06
"Cysteamine has been used by 81/102 patients (20 children started the therapy under 2 years of age)."( Report of a Brazilian multicenter study on nephropathic cystinosis.
Koch, VH; Vaisbich, MH, 2010
)
1.08
"Cysteamine (CS) has many biomedical and clinical applications because of its excellent water solubility, low cytotoxicity and good biocompatibility. "( Autophagy-mediated chemosensitization by cysteamine in cancer cells.
Man, N; Miao, YY; Wan, XM; Wen, LP; Zhang, L; Zheng, F, 2011
)
2.08
"Oral cysteamine has been shown to preserve renal function in these patients."( Intravenous delivery of cysteamine for the treatment of cystinosis: association with hepatotoxicity.
Bendel-Stenzel, MR; Dohil, R; Kim, Y; Steinke, J, 2008
)
1.11
"Cysteamine has beneficial effects in liver damaged by a variety of insults."( Effect of thiol-containing molecule cysteamine on the induction of inducible nitric oxide synthase in hepatocytes.
Ito, S; Kaibori, M; Kamiyama, Y; Matsui, K; Nishizawa, M; Okumura, T; Ozaki, T; Tanaka, H; Tokuhara, K,
)
1.13
"Cysteamine (CSH) has an inhibitory effect on the secretion of PRL, GH and TSH. "( Cysteamine acts immediately to inhibit prolactin release and induce cellular changes in estradiol-primed male rats.
Reifel, CW; Saunders, SL; Shin, SH, 1984
)
3.15
"Cysteamine has been reported to disturb learning performance in rats. "( Limited impairment of learning performances in mice treated with cysteamine.
Nakata, A; Nishiyama, N; Saito, H, 1995
)
1.97
"Cysteamine has a marked effect on gastric acid production and serum gastrin, even at the dose used in children with nephropathic cystinosis."( The effects of cysteamine on the upper gastrointestinal tract of children with cystinosis.
Murphy, JL; Wenner, WJ, 1997
)
1.37
"Cysteamine has been known to stimulate gastric acid secretion and to induce duodenal ulcers in rats. "( Evidence for a significant role of gastrin in cysteamine-induced hypersecretion of gastric acid.
Hayashi, N; Ikeda, M; Shimizu, K; Shiratori, K; Watanabe, S, 1997
)
2
"Cysteamine has been quantified in genital secretions and found in follicular fluids of all species tested."( Precursors of taurine in female genital tract: effects on developmental capacity of bovine embryo produced in vitro.
Guérin, P; Guillaud, J; Guyader-Joly, C; Ménézo, Y; Ponchon, S; Renard, JP, 1998
)
1.02
"(4) Cysteamine has many potential adverse effects, some of which are serious (mainly gastrointestinal and neuropsychiatric disorders)."( Cysteamine: new preparation. Chronic treatment of cystinosis.
, 1999
)
2.2
"Cysteamine has a marked influence on the activity of mainly aldolase F-1, 6-P and glucose-6-P dehydrogenase in red blood cells in vitro."( The influence of the known radioprotective compounds on the metabolism of human red blood cell. Part II. The influence of cysteamine on enzymic systems.
Chmiel, J; Kopczyński, Z; Rybczyńska, M, 1976
)
1.18
"Cysteamine, which has been reported to deplete SS content and to increase SS release in brain, augmented the basal and evoked release of ACh from hippocampal slices, without affecting SS-like content and release."( Evidence that somatostatin enhances endogenous acetylcholine release in the rat hippocampus.
Araujo, DM; Collier, B; Lapchak, PA; Quirion, R, 1990
)
1
"3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington's disease, prolactin-secreting adenomas) indications in clinical practice."( Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system.
Vécsei, L; Widerlöv, E, 1990
)
1.06
"Cysteamine and MPTP have been known to increase and decrease gastric acid secretion, respectively."( From cysteamine to MPTP: structure-activity studies with duodenal ulcerogens.
Cho, CH; Szabo, S, 1988
)
1.51
"Cysteamine has a biphasic effect in kindled rats. "( Induction and suppression of seizures by cysteamine in hippocampal kindled rats.
Cottrell, GA; Robertson, HA, 1986
)
1.98

Actions

Cysteamine is known to inhibit both bacterial and the eukaryotic host glycine cleavage systems via competitive inhibition of GLDC at concentrations lower than those required for direct antimicrobial or antiviral activity. Cysteamine can also increase an important antioxidant, glutathione.

ExcerptReferenceRelevance
"Cysteamine is known to inhibit both bacterial and the eukaryotic host glycine cleavage systems via competitive inhibition of GLDC at concentrations, lower than those required for direct antimicrobial or antiviral activity."( Cysteamine-mediated blockade of the glycine cleavage system modulates epithelial cell inflammatory and innate immune responses to viral infection.
Francis, ML; Fraser-Pitt, D; Mercer, DK; O'Neil, DA; Smith, DW; Toledo-Aparicio, D, 2023
)
3.07
"Cysteamine can also increase an important antioxidant, glutathione."( Therapeutic possibilities of cysteamine in the treatment of schizophrenia.
Lee, C; Pae, CU; Paik, IH, 2007
)
1.35
"Cysteamine does not inhibit the transferase-catalyzed conjugation of GSH and 1-chloro-2,4-dinitrobenzene."( The glutathione peroxidase activity of glutathione S-transferases.
Prohaska, JR, 1980
)
0.98
"Cysteamine was shown to produce a radioprotective effect in somatic cells of mus(2)201G1 and the control strain of drosophila which was manifested by the decreased incidence of cells with chromosome aberrations and diminished yield of deletions and exchanges."( [The modification of the radiation damage to the chromosomes in the somatic cells of radiosensitive Drosophila mutants. The radioprotective action of cysteamine].
Levina, VV; Malinovskiĭ, OV,
)
1.05
"The cysteamine-induced increase in gastric acid secretion was completely blocked by i.v."( Evidence for a significant role of gastrin in cysteamine-induced hypersecretion of gastric acid.
Hayashi, N; Ikeda, M; Shimizu, K; Shiratori, K; Watanabe, S, 1997
)
1.04
"The cysteamine-induced increase in glutathione was completely prevented by the gamma-glutamylcysteine synthetase inhibitor buthionine sulfoximine but was not affected by inhibition of homocysteine formation by 3-deazaaristeromycin."( Cysteamine increases homocysteine export and glutathione content by independent mechanisms in C3H/10T1/2 cells.
Djurhuus, R; Svardal, AM; Ueland, PM, 1990
)
2.2
"Cysteamine caused an increase in alkaline secretion in the rat during the first hour after administration, but rates after 5 and 20 h were the same as in controls and cysteamine (1 mg/ml) had no effect on secretion in vitro."( Cysteamine and propionitrile inhibit the rise of duodenal mucosal alkaline secretion in response to luminal acid in rats.
Bridén, S; Flemström, G; Kivilaakso, E, 1985
)
2.43

Treatment

Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome. Eyes treated with Cysteamine drops showed significantly less crystal accumulation compared to control eyes.

ExcerptReferenceRelevance
"Cysteamine treatment ameliorates this phenotype, except for abnormalities in apoptosis and basal autophagy."( Use of Human Induced Pluripotent Stem Cells and Kidney Organoids To Develop a Cysteamine/mTOR Inhibition Combination Therapy for Cystinosis.
D'Souza, RF; Davidson, AJ; Harrison, PT; Hollywood, JA; Holm, TM; Przepiorski, A; Sreebhavan, S; Wolvetang, EJ, 2020
)
1.51
"Cysteamine-treated transgenic mice displayed significant improvements in motor performance as compared to saline-treated transgenic littermates."( Beneficial effects of cysteamine in Thy1-α-Syn mice and induced pluripotent stem cells with a SNCA gene triplication.
Alpaugh, M; Chen, X; Cicchetti, F; David, LS; Durcan, T; Lauinger, N; Saint-Pierre, M; Siddu, A, 2020
)
1.59
"In cysteamine-treated mice, fibrosis severity decreased significantly at 14 and 21 days after unilateral ureteral obstruction, and renal oxidized protein levels decreased at each time point, suggesting reduced oxidative stress."( Cysteamine modulates oxidative stress and blocks myofibroblast activity in CKD.
Bahrami, NM; Barshop, BA; Duffield, JS; Eddy, AA; Gangoiti, JA; Lopez-Guisa, JM; Okamura, DM; Pasichnyk, K; Ren, S; Williams, JM; Yamaguchi, I, 2014
)
2.36
"Cysteamine treatment should be started as early as possible, and dosage should be monitored and adapted based on trough WBC cystine levels."( Management dilemmas in pediatric nephrology: Cystinosis.
Besouw, MT; Cassiman, D; Claes, KJ; Levtchenko, EN; Van Dyck, M, 2015
)
1.86
"Cysteamine treatment increased total glutathione in both control and cystinotic cells and normalized cystine levels and glutathione redox status in cystinotic cells."( Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells.
Kluijtmans, LA; Levtchenko, EN; Masereeuw, R; Monnens, LA; Scheffer, PG; van den Heuvel, LP; van der Velden, TJ; Willems, PH; Wilmer, MJ, 2011
)
2.53
"Cysteamine-treated cells evidenced higher viability relative to the controls at 5 mM tBHP, and cysteamine also effectively protected HCECs against ROS-induced cell death via an increase in intracellular glutathione."( Effect of cysteamine on oxidative stress-induced cell death of human corneal endothelial cells.
Chung, TY; Hyon, JY; Seo, JM; Shin, YJ; Wee, WR, 2011
)
1.49
"Cysteamine pre-treatment decreased baseline CA1 population spike amplitude following high intensity stimulation of Schaffer collaterals."( Cysteamine pre-treatment reduces pentylenetetrazol-induced plasticity and epileptiform discharge in the CA1 region of rat hippocampal slices.
Fathollahi, Y; Hajizadeh, S; Mirnajafizadeh, J; Rostampour, M; Semnanian, S; Shafizadeh, M, 2002
)
2.48
"Cysteamine treatment was without effect on insulin and glucagon release under the conditions tested."( Cysteamine blocks somatostatin secretion without altering the course of insulin or glucagon release. A new model for the study of islet function.
Elde, RP; Grouse, LH; Sorenson, RL, 1983
)
2.43
"Cysteamine treatment resulted in gastric acid hypersecretion, which was largely abolished by concurrent cimetidine administration."( Mucosal enzyme activities, with special reference to enzymes implicated in bicarbonate secretion, in the duodenum of rats with cysteamine-induced ulcers.
Murray, DJ; Peters, TJ; Stiel, D, 1983
)
1.19
"Cysteamine pretreatment of both normal and cystinotic cells resulted in an initial increased conversion of exogenous cystine to intracellular cysteine."( Handling of L-[35S]cystine by cysteamine-pretreated cystinotic and normal fibroblasts.
Lee, J; Segal, S; States, B, 1983
)
1.28
"Cysteamine treated mice rather than rats are advocated for screening purposes since less test compound is required."( The effect of atropine, cimetidine and FPL 52694 on duodenal ulcers in mice.
Smith, JA, 1983
)
0.99
"Cysteamine treatment inhibited both expression of the IL-2 mRNA and secretion of IL-2 into the culture medium."( Transcription factors as targets for oxidative signalling during lymphocyte activation.
Fragonas, JC; Goldstone, SD; Hunt, NH; Jeitner, TM, 1995
)
1.01
"In cysteamine-treated rats, neither the strongly bound tetramers of 340 kD nor dimers of 185 kD were found by gel filtration."( Abnormal glycosylation of duodenal membranous alkaline phosphatase induced by cysteamine in rats.
Japundzic, I; Kosaric, B, 1994
)
1.03
"In cysteamine-treated rats (250 mg/kg weight, intramuscular injection), mucosal alkaline secretion by intravenous EGF (10 micrograms/kg/hr) increased significantly only at levels of high luminal acidity, whereas that by intraduodenal EGF (10 micrograms/kg/hr) increased greatly at both high and low luminal acidities."( Effects of epidermal growth factor on alkaline secretion and mucus formation in rat duodenum exposed to luminal acid.
Yoshikawa, I, 1993
)
0.8
"Cysteamine treatment drastically reduced somatostatin immunoreactivity in the cochlear nuclear complex and the caudal pontine reticular nucleus, i.e."( Cysteamine impairs the development of the acoustic startle response in rats: possible role of somatostatin.
Friauf, E; Koch, M; Kungel, M, 1996
)
2.46
"Cysteamine treatment induced a reduction of the number of dendritic end points by more than 50%."( Influence of the neuropeptide somatostatin on the development of dendritic morphology: a cysteamine-depletion study in the rat auditory brainstem.
Friauf, E; Kungel, M; Piechotta, K; Rietzel, HJ, 1997
)
1.24
"The cysteamine-treated animals exhibited significant impairment in spatial learning as determined using a three-panel runway task."( Acceleration of ageing-related gliopathic changes and hippocampal dysfunction following intracerebroventricular infusion of cysteamine in adult rats.
Chapman, A; Lacaille, JC; Mohr, G; Schipper, HM; St-Jacques, R, 1999
)
0.99
"Cysteamine treatment increased the development of ER-negative tumors."( Inhibitory effects of WR-2721 and cysteamine on tumor initiation in mammary glands of pregnant rats by radiation.
Inano, H; Kobayashi, H; Onoda, M; Suzuki, K; Wakabayashi, K, 2000
)
1.31
"Cysteamine treatment completely prevented the curtailment of NADPH-cytochrome c reductase and glucose 6-phosphatase activities in the protected group, and partially maintained aniline hydroxylase activity."( Experimental acetaminophen-induced hepatic necrosis: biochemical and electron microscopic study of cysteamine protection.
Bhakthan, NM; Chiu, S, 1978
)
1.2
"Cysteamine pretreatment with a dose of 150 mg/kg slightly increased the dopamine, and markedly decreased the noradrenaline, content of the hypothalamus in a dose-related manner."( Dose-related effects of cysteamine treatment on hypothalamic and striatal dopamine, noradrenaline and serotonin neurotransmission.
Bollók, I; Faludi, M; Kovács, GL; Telegdy, G; Vécsei, L, 1985
)
1.3
"Cysteamine pretreatment of rats (depletion of somatostatin containing D-cells and decrease in somatostatin secretion) did not change the Met-enkephalin effect on insulin secretion."( The significance of mu- and delta-receptors in rat pancreatic islets for the opioid-mediated insulin release.
Ammon, HP; Berger, U; Verspohl, EJ, 1986
)
0.99
"In cysteamine-treated rats a marked decrease in SOM-28(15-28)-like immunoreactivity (1.1) could be recorded subjectively at all antibody concentrations in fibers in several brain areas, including nucleus accumbens, tuberculum olfactorium and the hypothalamic ventromedial and arcuate nuclei."( Immunohistochemical analysis of the effects of cysteamine on somatostatin-like immunoreactivity in the rat central nervous system.
Brownstein, M; Ceccatelli, S; Elde, R; Hallman, H; Hökfelt, T; Nylander, I; Terenius, L,
)
0.9
"Cysteamine (90 mg/kg) treatment given s.c."( Role of somatostatin in the regulation of vasopressin secretion.
Brown, MR; Crum, R; Mortrud, M; Sawchenko, P, 1988
)
1
"Cysteamine treatment (8.5 months) did not affect hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activity compared with controls."( Effect of chronic cysteamine treatment on mouse liver aryl hydrocarbon hydroxylase activity.
Peterson, TC, 1988
)
1.33
"Cysteamine treatment does not alter nursing behavior of the mothers."( Effect of cysteamine on suckling-induced prolactin secretion in the rat.
Millard, WJ; O'Sullivan, D; Riskind, PN, 1987
)
1.4
"Treatment with cysteamine 5% cream over 4 months resulted in significant improvement with a reduction in the melanin index."( A case report on the use of topical cysteamine 5% cream in the management of refractory postinflammatory hyperpigmentation (PIH) resistant to triple combination cream (hydroquinone, topical corticosteroids, and retinoids).
Balogun, M; Mathe, N; Yoo, J, 2021
)
1.24
"Treatment with cysteamine was safe and well tolerated."( A randomized, double-blind, placebo-controlled trial evaluating cysteamine in Huntington's disease.
Allain, P; Azulay, JP; Bachoud-Lévi, AC; Bonneau, D; Calvas, F; Charles, P; Durr, A; Goizet, C; Krystkowiak, P; Maison, P; Olivier, A; Prundean, A; Reynier, P; Saudou, F; Scherer, C; Simonin, C; Tranchant, C; Verny, C; von Studnitz, E; Youssov, K, 2017
)
1.03
"Oral treatment with cysteamine resulted in improvement of renal function to CKD stage 3."( [Nephropatic cystinosis: report of one case].
Grandy, J; Krall, P; Nualart, D, 2018
)
0.8
"Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome."( Management of bone disease in cystinosis: Statement from an international conference.
Ariceta, G; Awan, A; Bacchetta, J; Bechtold, S; Bergmann, C; Cassidy, N; Deschenes, G; Elenberg, E; Gahl, WA; Greil, O; Haffner, D; Harms, E; Herzig, N; Hohenfellner, K; Hoppe, B; Koeppl, C; Levtchenko, E; Lewis, MA; Nesterova, G; Rauch, F; Santos, F; Schlingmann, KP; Servais, A; Soliman, NA; Steidle, G; Sweeney, C; Topaloglu, R; Treikauskas, U; Tsygin, A; V Vigier, R; Veys, K; Zustin, J, 2019
)
0.85
"Eyes treated with cysteamine drops showed significantly less crystal accumulation compared to control eyes (p<0.001) with only a 15% increase in treated eyes (p=ns) compared to 173% increase (p<0.04) for untreated eyes."( Evaluation of topical cysteamine therapy in the CTNS(-/-) knockout mouse using in vivo confocal microscopy.
Flynn, KJ; Jester, JV; Nien, CJ; Simpson, JL, 2011
)
1.01
"Treatment with cysteamine, a TG2 inhibitor, ameliorated disease severity in WT mice."( Transglutaminase 2 exacerbates experimental autoimmune encephalomyelitis through positive regulation of encephalitogenic T cell differentiation and inflammation.
Byoun, OJ; Lee, DS; Oh, K; Park, HB; Seo, MW, 2012
)
0.72
"Treatment with cysteamine favours the transport of cystine out of the lysosomes, diminishes organ damage, and postpones the progression of renal failure."( Follow-up and treatment of adults with cystinosis in the Netherlands.
Geelen, JM; Levtchenko, EN; Monnens, LA, 2002
)
0.65
"Pretreatment with cysteamine (30 mg/100 g BW, sc, 4 h previously) or anti-SRIF rabbit serum (0.5 ml/rat, iv, 1 h previously) raised basal plasma GH levels and markedly exaggerated the plasma GH response to hpGRF (1-44) (80 ng/100 g BW, iv)."( Inhibition by gastrin-releasing peptide of growth hormone (GH) secretion induced by human pancreatic GH-releasing factor in rats.
Imura, H; Kabayama, Y; Kato, Y; Ohta, H; Shimatsu, A; Yanaihara, N, 1984
)
0.59
"Pretreatment with cysteamine (100 mg/kg) inhibited the ability of the duodenal surface epithelium to respond to luminal acid with a compensatory rise in alkaline secretion."( Stimulation by BW755C and inhibition by cysteamine of duodenal epithelial alkaline secretion suggest a role of endogenous prostaglandin in mucosal protection.
Bridén, S; Flemström, G; Kivilaakso, E, 1984
)
0.86
"Treatment with cysteamine protected against the fall in soluble SH groups in heart tissue."( Regulatory role of glutathione and soluble sulfhydryl groups in the toxicity of adriamycin.
Boerth, RC; Freeman, RW; Harbison, RD; MacDonald, JS; Oates, JA; Olson, RD; Slonim, AE; vanBoxtel, CJ, 1980
)
0.6
"Treatment with cysteamine (50, 100, 200 mg/kg, s.c.), a depletor of somatostatin, significantly and dose-dependently reduced the retention of single trial passive avoidance task."( Possible involvement of brain somatostatin in the memory formation of rats and the cognitive enhancing action of FR121196 in passive avoidance task.
Maeda, N; Matsuoka, N; Satoh, M; Yamaguchi, I, 1994
)
0.63
"Rats treated with cysteamine showed a high frequency and severity of duodenal ulcer, and the calcium content in the duodenal mucosa was elevated."( Relationship between tissue calcium content and duodenal ulcer in the rat.
Chen, G; Liu, S; Yuan, S; Zhang, Z, 1993
)
0.61
"Pretreatment with cysteamine (200 mg/kg, s.c.) significantly attenuated the penile erection induced by fenfluramine and apomorphine, but scarcely affected that induced by pilocarpine."( Brain somatostatin depletion by cysteamine attenuates the penile erection induced by serotonergic and dopaminergic, but not by cholinergic, activation in rats.
Maeda, N; Matsuoka, N; Yamaguchi, I; Yamazaki, M, 1996
)
0.9
"Treatment with cysteamine and kidney transplantation enables cystinotic girls to reach reproductive age and to be healthy enough to permit pregnancy."( Evaluation of the reproductive and developmental safety of cysteamine in the rat: effects on female reproduction and early embryonic development.
Assadi, FK; Beckman, DA; Mullin, JJ,
)
0.71
"(6) Treatment with cysteamine is expensive."( Cysteamine: new preparation. Chronic treatment of cystinosis.
, 1999
)
2.06
"Treatment with cysteamine, which caused a somatostatin depletion in the brain, was required to observe labeling in the hypothalamus."( Localization and characterization of brain somatostatin receptors as studied with somatostatin-14 and somatostatin-28 receptor radioautography.
Leroux, P; Pelletier, G; Quirion, R, 1985
)
0.61
"Pretreatment with cysteamine (300 mg/kg, s.c.), a known depletor of hypothalamic SRIF, or with anti-SRIF serum (0.5 ml/rat) completely counteracted the lessening of the GH response to GHRH induced by 2.0 micrograms GH injected i.c.v."( Involvement of the somatostatin and cholinergic systems in the mechanism of growth hormone autofeedback regulation in the rat.
Camanni, F; Caroleo, MC; Cermenati, P; Ghigo, E; Locatelli, V; Müller, EE; Panzeri, G; Torsello, A, 1988
)
0.6
"Pretreatment with cysteamine 5 min prior to dexamethasone, while having no significant effect on basal corticosterone levels, completely blocked the dexamethasone-induced suppression of corticosterone levels."( Effects of systemic and intracerebroventricular cysteamine on dexamethasone-induced suppression of corticosterone levels in the rat.
Radke, JM; Vincent, SR, 1988
)
0.85

Toxicity

N-Acetylcysteine (NAC) is protective against acetaminophen-induced hepatotoxicity. It has been shown that unithiol diminishes toxic action of cysteamine, AET, and disulfide of WR-1065.

ExcerptReferenceRelevance
" Toxicity is likely to occur after a minimum ingestion of 140 mg/kg, but the toxic dose may vary as a function of individual glutathione levels."( Toxicity of acetaminophen overdose.
Peterson, RG; Rumack, BH, 1978
)
0.26
"The rationale for melanoma-specific antitumor agents containing phenolic amines is based in part on the ability of the enzyme tyrosinase to oxidize these prodrugs to toxic intermediates."( Thymidylate synthase as a target enzyme for the melanoma-specific toxicity of 4-S-cysteaminylphenol and N-acetyl-4-S-cysteaminylphenol.
Bloomer, WD; Prezioso, JA; Wang, N, 1992
)
0.28
"N-Acetylcysteine (NAC) is protective against acetaminophen-induced hepatotoxicity primarily by providing precursor for the glutathione synthetase pathway, while cysteamine has been demonstrated to alter the cytochrome P-450 dependent formation of toxic acetaminophen metabolite."( Cysteamine in combination with N-acetylcysteine prevents acetaminophen-induced hepatotoxicity.
Brown, IR; Peterson, TC, 1992
)
1.92
" We propose that m-dinitrobenzene requires metabolic activation before it can exert its toxicity to Sertoli cells, and it appears that the toxic species is m-nitrosonitrobenzene or a further metabolite of m-nitrosonitrobenzene."( Modulation of m-dinitrobenzene and m-nitrosonitrobenzene toxicity in rat Sertoli--germ cell cocultures.
Cave, DA; Foster, PM, 1990
)
0.28
" Centrilobular hepatic necrosis and elevation in transaminase activity following a toxic dose of acetaminophen were prevented by treatment with cysteamine."( The role of heme oxygenase and aryl hydrocarbon hydroxylase in the protection by cysteamine from acetaminophen hepatotoxicity.
Peterson, MR; Peterson, TC; Williams, CN, 1989
)
0.7
" Since cysteamine decreased both beta and the apparent rate constant for mercapturate formation (K'MA), the proportion of the dose of acetaminophen which is converted to the toxic metabolite (K'MA/beta) was not significantly decreased in the presence of cysteamine."( Acetaminophen hepatotoxicity: studies on the mechanism of cysteamine protection.
Jollow, DJ; Miller, MG, 1986
)
0.97
" In contrast, radiochromatograms obtained from cells treated with toxic levels of MISO (75 mM) under aerobic conditions indicated no drug metabolism."( Sulphydryls, ascorbate and oxygen as modifiers of the toxicity and metabolism of misonidazole in vitro.
Rauth, AM; Taylor, YC, 1980
)
0.26
"It has been shown that unithiol diminishes toxic action of cysteamine, AET, and disulfide of WR-1065 on mice."( [Decrease of toxic effects of aminothiol radiation-protective agents and increase of chemical protection action against ionizing radiation by the use of unithiol].
Bol'shakova, OI; Grachev, SA; Korolva, IK; Nikanorova, NG; Sverdlov, AG,
)
0.37
" It is important to define the mechanism of toxicity so that means can be devised to ameliorate the toxic effects in order to produce safer usage."( The myelotoxicity of chloramphenicol: in vitro and in vivo studies: I. In vitro effects on cells in culture.
Fairbairn, A; Harvey, D; Holt, DE; Hurley, R; Ryder, TA, 1997
)
0.3
" It is not known whether exposure to cysteamine will have adverse effects on reproduction in the human."( Evaluation of the reproductive and developmental safety of cysteamine in the rat: effects on female reproduction and early embryonic development.
Assadi, FK; Beckman, DA; Mullin, JJ,
)
0.65
" Cysteamine produced dose-dependent developmental toxicity with an apparent no adverse effect observed level of 75 mg/kg/day."( Developmental toxicity of cysteamine in the rat: effects on embryo-fetal development.
Assadi, FK; Beckman, DA; Mullin, JJ,
)
1.34
" The latter is the major undesired side-effect of almost all NSAIDs."( Reduction of gastrointestinal toxicity of NSAIDs via molecular modifications leading to antioxidant anti-inflammatory drugs.
Galanakis, D; Kourounakis, AP; Kourounakis, PN; Tsiakitzis, K, 2000
)
0.31
" CCRF-CEM cells have no catalase activity, so the inhibition of glutathione peroxidase may sensitize these cells to the less than toxic levels of peroxide generated by this aminothiol."( Mechanisms for the cytotoxicity of cysteamine.
Jeitner, TM; Lawrence, DA, 2001
)
0.59
"To report new adverse effects of cysteamine."( Cysteamine toxicity in patients with cystinosis.
Besouw, MT; Bowker, R; Dutertre, JP; Emma, F; Gahl, WA; Greco, M; Levtchenko, EN; Lilien, MR; McKiernan, J; Nobili, F; Schneider, JA; Skovby, F; van den Heuvel, LP; Van't Hoff, WG, 2011
)
2.09
"New adverse events were reported in 8 of 550 patients with cystinosis treated with cysteamine in Europe during the last 5 years."( Cysteamine toxicity in patients with cystinosis.
Besouw, MT; Bowker, R; Dutertre, JP; Emma, F; Gahl, WA; Greco, M; Levtchenko, EN; Lilien, MR; McKiernan, J; Nobili, F; Schneider, JA; Skovby, F; van den Heuvel, LP; Van't Hoff, WG, 2011
)
2.04
" Our goal is to design a lens that is safe and that can deliver a daily therapeutic dose of cysteamine to the cornea while retaining drug stability."( In vitro drug release and in vivo safety of vitamin E and cysteamine loaded contact lenses.
Bhattacharya, A; Chauhan, A; Dixon, P; Fentzke, RC; Hazra, S; Konar, A, 2018
)
0.95
" Another newer, viscous formulation, Cystadrops, performed better than the standard formulation in terms of change in CCCS, IVCM score, corneal crystal depth, and photophobia score; however, local adverse effects and blurring were higher in the group receiving Cystadrops."( Efficacy and Safety of Topical Cysteamine in Corneal Cystinosis: A Systematic Review and Meta-Analysis.
Avti, P; Bhattacharyya, A; Bhattacharyya, J; Das, D; Kaur, H; Kaur, S; Kumar, S; Medhi, B; Prajapat, M; Prakash, A; Ram, J; Sarma, P; Shekhar, N; Singh, R, 2021
)
0.91
" Original studies that reported pre- and post-treatment Melasma Area Severity Index (MASI)/modified Melasma Area Severity Index (mMASI) scores and/or adverse effects (AEs) were eligible for inclusion."( Efficacy and safety of topical agents in the treatment of melasma: What's evidence? A systematic review and meta-analysis.
Aljabban, A; Bain, PA; Bay, CP; Chang, YF; Chung, HJ; Desai, SR; Lee, TL; Oyerinde, O, 2023
)
0.91
" This provides a perspective on the safety of cysteamine administration in children and identifies potential targets for protection against adverse reactions."( Hepatic lipid metabolism disorders and immunotoxicity induced by cysteamine in early developmental stages of zebrafish.
Bi, Y; Cao, Z; Chen, C; Chen, J; Hu, H; Li, X; Liao, X; Liu, F; Lu, H; Xiong, G; Yang, D; Zhang, L; Zhong, Z; Zuo, Y, 2023
)
1.41

Pharmacokinetics

The delayed tmax following cysteamine bitartrate enteric-coated suggested that the cysteamines was released enterically. Blood samples were collected and analysed for plasma Cysteamine and white blood cell cystine content.

ExcerptReferenceRelevance
" Pharmacokinetic parameters were estimated by compartmental modeling of plasma concentration data from 10-min and 120-min iv infusions."( Pharmacokinetics and disposition of WR-1065 in the rhesus monkey.
Fleckenstein, L; Geary, RS; Huelle, BK; Ludden, TM; Mangold, DJ; Miller, MA; Sanchez-Barona, DO; Swynnerton, NF,
)
0.13
" Blood samples were collected and analysed for plasma cysteamine and white blood cell cystine content and pharmacokinetic and pharmacodynamic parameters estimated by NONMEM analysis using a linked pharmacokinetic-pharmacodynamic model."( Steady-state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in paediatric nephropathic cystinosis patients.
Belldina, EB; Brundage, RC; Huang, MY; Schneider, JA; Tracy, TS, 2003
)
0.82
"The pharmacokinetic data generated help extend our understanding of cysteamine."( Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion.
Barshop, BA; Deutsch, R; Dohil, R; Fidler, MC; Gangoiti, JA; Martin, M; Schneider, JA, 2007
)
0.9
"This is the only study that provides pharmacokinetic data for cysteamine delivered in an enteric-release preparation in normal subjects."( Pharmacokinetics of enteric-coated cysteamine bitartrate in healthy adults: a pilot study.
Barshop, BA; Cabrera, BL; Dohil, R; Fidler, M; Gangoiti, JA; Schneider, JA, 2010
)
0.88
" The tmax following cysteamine bitartrate non-enteric-coated (mean and SD is 75+/-19 min) was shorter than cysteamine bitartrate enteric-coated (220+/-74 min) (P=0."( Pharmacokinetics of enteric-coated cysteamine bitartrate in healthy adults: a pilot study.
Barshop, BA; Cabrera, BL; Dohil, R; Fidler, M; Gangoiti, JA; Schneider, JA, 2010
)
0.96
" The delayed tmax following cysteamine bitartrate enteric-coated suggested that the cysteamine was released enterically."( Pharmacokinetics of enteric-coated cysteamine bitartrate in healthy adults: a pilot study.
Barshop, BA; Cabrera, BL; Dohil, R; Fidler, M; Gangoiti, JA; Schneider, JA, 2010
)
0.93
" A total of 250 cysteamine plasma concentrations and 243 intracellular cystine concentrations were used to perform a population pharmacokinetic and pharmacodynamic analysis."( Population pharmacokinetics and pharmacodynamics of cysteamine in nephropathic cystinosis patients.
Bouazza, N; Chadefaux-Vekemans, B; Deschenes, G; Niaudet, P; Ottolenghi, C; Ricquier, D; Tréluyer, JM; Urien, S, 2011
)
0.97
" The Cmax was achieved in 5-10 min from PV and 5-22."( Pharmacokinetics of cysteamine bitartrate following intraduodenal delivery.
Barshop, BA; Cabrera, BL; Dohil, R; Gangoiti, JA; Rioux, P, 2014
)
0.73
" Therefore, there is a need for a cysteamine formulation with an improved pharmacokinetic profile."( A novel sustained-release cysteamine bitartrate formulation for the treatment of cystinosis: Pharmacokinetics and safety in healthy male volunteers.
Berends, CL; Bergmann, KR; Büller, H; Burggraaf, J; de Leede, LGJ; de Loos, F; de Visser, SJ; de Vries, WS; Kamerling, IMC; Klarenbeek, NB; Moerland, M; Pagan, L; van der Wel, V; van Esdonk, MJ; Waals, H, 2021
)
1.2

Compound-Compound Interactions

The effectiveness of the histamine H2-receptor antagonist SKF 93479 in preventing gizzard ulcerations when given in combination with cysteamine-HCl was also examined.

ExcerptReferenceRelevance
" Neither decrease in plasma acetaminophen levels nor depression of cytochrome P-450 enzyme activity appears to be the mechanism of protection when these doses of NAC, cysteamine, or both drugs together are administered with a toxic dose of acetaminophen in mice."( Cysteamine in combination with N-acetylcysteine prevents acetaminophen-induced hepatotoxicity.
Brown, IR; Peterson, TC, 1992
)
1.92
"To investigate effects of dietary caloric restriction (DR) combined with antioxidant feeding, long-lived hybrid mice were divided into four dietary groups at weaning, and followed until natural death."( Dietary restriction alone and in combination with oral ethoxyquin/2-mercaptoethylamine in mice.
Harris, SB; Mickey, MR; Smith, GS; Walford, RL; Weindruch, R, 1990
)
0.28
" The effectiveness of the histamine H2-receptor antagonist, SKF 93479, in preventing gizzard ulcerations when given in combination with cysteamine-HCl was also examined."( Gizzard ulceration in chicks fed cysteamine alone or in combination with a histamine H2-receptor antagonist.
Hedde, RD; Lindsey, TO; Zavy, MT, 1988
)
0.76

Bioavailability

Cysteamine bitartrate and phosphocysteamine may have a better bioavailability than cysteamine hydrochloride. HEC-cysteamine could be a promising excipient for nanoparticulate delivery systems for poorly absorbed drugs.

ExcerptReferenceRelevance
" The high bioavailability of Se from selenite found by others might thus be the result of the presence of thiols in the gastrointestinal tract."( Stimulation of mucosal uptake of selenium from selenite by some thiols at various sites of rat intestine.
Scharrer, E; Senn, E; Wolffram, S,
)
0.13
" It has been suggested that cysteamine bitartrate and phosphocysteamine are better tolerated and may have a better bioavailability than cysteamine hydrochloride."( A study of the relative bioavailability of cysteamine hydrochloride, cysteamine bitartrate and phosphocysteamine in healthy adult male volunteers.
Chaumet-Riffaud, P; Daurat, V; Funck-Brentano, C; Tennezé, L; Tibi, A, 1999
)
0.86
"We compared the pharmacokinetics and tolerance of these three formulations of cysteamine in 18 healthy adult male volunteers in a double-blind, latin-square, three-period, single oral dose cross-over relative bioavailability study."( A study of the relative bioavailability of cysteamine hydrochloride, cysteamine bitartrate and phosphocysteamine in healthy adult male volunteers.
Chaumet-Riffaud, P; Daurat, V; Funck-Brentano, C; Tennezé, L; Tibi, A, 1999
)
0.79
" The present study demonstrates that these new N-isobutyryl derivatives, which are expected to have a greater bioavailability than their acetyl analogues, may have useful applications in HIV infection in respect to their antioxidant and anti-HIV activities."( Synthesis of new N-isobutyryl-L-cysteine/MEA conjugates: evaluation of their free radical-scavenging activities and anti-HIV properties in human macrophages.
Clayette, P; Mialocq, P; Oiry, J; Smietana, M; Vasseur, JJ, 2008
)
0.35
" Little is known about the bioavailability and biodistribution of the drug."( Pharmacokinetics of cysteamine bitartrate following intraduodenal delivery.
Barshop, BA; Cabrera, BL; Dohil, R; Gangoiti, JA; Rioux, P, 2014
)
0.73
" Accordingly, HEC-cysteamine could be a promising excipient for nanoparticulate delivery systems for poorly absorbed drugs."( Thiolated hydroxyethyl cellulose: design and in vitro evaluation of mucoadhesive and permeation enhancing nanoparticles.
Barthelmes, J; Bernkop-Schnürch, A; Martien, R; Müller, C; Rahmat, D; Shahnaz, G, 2013
)
0.72
" The mathematical modeling of drug transport in the eye suggested that the vitamin E loaded contact lens can provide the daily therapeutic dose without causing toxicity, while significantly increasing the bioavailability compared to eye drops."( Feasibility of corneal drug delivery of cysteamine using vitamin E modified silicone hydrogel contact lenses.
Chauhan, A; Fentzke, RC; Hsu, KH, 2013
)
0.66
"Administration of macromolecule compositions in medicine and cosmetics always exhibited low bioavailability due to the limitation of transmembrane transport."( Fusion with pep-1, a cell-penetrating peptide, enhances the transmembrane ability of human epidermal growth factor.
Gu, XC; He, YY; Li, W; Li, XM; Luo, XG; Ma, DY; Wang, CX; Wang, Y; Zhang, TC; Zhou, H, 2016
)
0.43
" Esterification of the thiol conferred oxidative stability, while sufficient lipophilicity for oral bioavailability was achieved by acylation of the α-carboxyl group of γ-glutamyl-cysteamine (4)."( Synthesis of diacylated γ-glutamyl-cysteamine prodrugs, and in vitro evaluation of their cytotoxicity and intracellular delivery of cysteamine.
Anderson, RJ; Cannell, SJ; Frost, L; Groundwater, PW; Hambleton, PA; Suryadevara, P, 2016
)
0.9
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

Cysteamine treatment should be started as early as possible, and dosage should be monitored and adapted based on trough WBC cystine levels. Repeated injections of pentagastrin in a dosage inducing an acid response equivalent to the one induced by cysteamine did not produce any histologic changes in Brunner's glands or any ulcerations.

ExcerptRelevanceReference
" One group of golden Syrian hamsters was administered a toxic dosage of acetaminophen (600 mg ."( Experimental acetaminophen-induced hepatic necrosis: biochemical and electron microscopic study of cysteamine protection.
Bhakthan, NM; Chiu, S, 1978
)
0.47
" Atropine methylbromide inhibited duodenal ulcers induced by cysteamine dose-dependently and pyloric ligation immediately prior to cysteamine dosing completely inhibited ulceration."( Influence of various factors and drugs on cysteamine-induced duodenal ulcers in the rat.
Fujii, Y; Ishii, Y, 1975
)
0.76
" This sensitive and specific assay helped in controlling compliance and adjusting dosage regimen in each patient."( [Intra-leukocyte cystine in cystinosis treated with cysteamine].
Broyer, M; Ged, C; Jean, G; Kamoun, P; Tete, MJ, 1991
)
0.53
" When the initial slopes of the dose-response curves are used to compare the relative biological effectiveness (RBE) of different radiocompounds, the alpha particles emitted in the decay of 210Po are more effective than Auger electrons emitted by 125I incorporated in the DNA of the spermatogonial cells, and both emissions are more effective than X rays."( Induction of sperm head abnormalities by incorporated radionuclides: dependence on subcellular distribution, type of radiation, dose rate, and presence of radioprotectors.
Howell, RW; Lanka, VK; Narra, VR; Rao, DV; Sastry, KS, 1991
)
0.28
" Furthermore, elicitation of seizures 4 h after cysteamine enhanced its anticonvulsant effects at 1 day after the drug, causing a parallel left shift of the dose-response curve."( Time-dependent pro- and anticonvulsant effects of cysteamine on the development and expression of amygdaloid kindled seizures.
Abraham, WC; Bilkey, DK; Takazawa, A, 1990
)
0.79
" In conclusion, the effectiveness of cysteamine seems obvious in this group of patients if rigorous compliance with the drug dosing schedule is achieved."( [Treatment of cystinosis using cysteamine].
Broyer, M; Tete, MJ, 1990
)
0.84
" Administration of bromocriptine alone at either dosage had no influence on gastric carcinogenesis."( Attenuating effect of bromocriptine on cysteamine anticarcinogenesis of stomach cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine.
Baba, M; Ichii, M; Iishi, H; Nakaizumi, A; Taniguchi, H; Tatsuta, M; Uehara, H, 1990
)
0.55
" In this manner, complete dose-response curves could be obtained from one plate."( Rapid fluorescence-based assay for radiosensitivity and chemosensitivity testing in mammalian cells in vitro.
Begg, AC; Mooren, E, 1989
)
0.28
" Four series of experiments were undertaken using in vitro cell suspensions, namely: (1) determination of the effect of cysteamine concentration on cell growth; (2) determination of the temperature dependence of ultrasonically induced cell damage; (3) determination of a dose-response relationship for the cytotoxicity of cysteamine; and (4) assessment of cell integrity and reproductive capacity in the presence or absence of cysteamine during ultrasonic exposure."( Confirmation of the protective effect of cysteamine in in vitro ultrasound exposures.
Brayman, A; Church, CC; Inoue, M; Malcuit, MS; Miller, MW, 1989
)
0.75
" the respective ED50s calculated from the previously established dose-response curves) of all the three antagonists was completely different."( The effect of the new H2-receptor antagonist mifentidine on gastric secretion, gastric emptying and experimental gastric and duodenal ulcers in the rat: comparison with cimetidine and ranitidine.
Del Soldato, P; Scarpignato, C; Tangwa, M; Tramacere, R, 1986
)
0.27
" Maximum tolerated dosage for 2 weeks produced no consistent change in extrapyramidal or dementia scores."( Huntington's disease: effect of cysteamine, a somatostatin-depleting agent.
Barone, P; Chase, TN; Fedio, P; Juncos, J; Mohr, E; Serrati, C; Shults, C; Steardo, L; Tamminga, CA, 1986
)
0.55
" However, its efficacy in restoring muscle carnitine to normal, and the optimal dosage regimen, have yet to be determined."( Oral carnitine therapy in children with cystinosis and renal Fanconi syndrome.
Bernar, J; Bernardini, I; Dalakas, M; Gahl, WA; Harper, GS; Hoeg, JM; Hurko, O; Rizzo, WB, 1988
)
0.27
" w) at a dosage of 400 mg/kg."( [Small intestinal alkaline phosphatase activity and changes induced by cysteamine administration in fecal excretions of male Wistar rats].
Hosoya, N; Kim, SH; Shidoji, Y, 1988
)
0.51
" Two assumptions were made: human radiosensitivity equals that of the mouse; and dose-response is linear."( [Assessment of the genetic risk of radiation by irradiation data from laboratory mammals].
Baĭrakova, AK; Benova, DK; Kusheva, RP; Rupova, IM; Vŭglenov, AK, 1985
)
0.27
" Linear dose-response curves were obtained for both dose ranges."( Quantitative measurement of DNA strand breaks and repair in gamma-irradiated human leukocytes from normal and ataxia telangiectasia donors.
Duranton, I; Magdelenat, H; Moustacchi, E; Rigaud, O; Thierry, D, 1985
)
0.27
" The objectives of this investigation were to: (1) determine the dose-response and time course of DBH inhibition by MEA in vivo and in vitro, and correlate these findings with MEA tissue levels and (2) assess the function of SRIF and NE/EPI in regulation of episodic GH and TSH secretion using MEA."( Cysteamine effects on monoamines, dopamine-beta-hydroxylase and the hypothalamic-pituitary axis.
Craig, R; Terry, LC, 1985
)
1.71
" Although the data demonstrate stimulation of gastric output of acid and pepsin by certain doses of cysteamine or propionitrile, cysteamine produced dose-response increases in acid secretion only during the 1st hour following administration."( Secretory changes associated with chemically-induced duodenal ulceration: simultaneous measurements of acid, pepsin, base and pancreatic enzymes in rats with chronic gastric fistula.
Gallagher, GT; Szabo, S, 1984
)
0.48
" showed moderate effects, but the dosage also inhibited cysteamine-stimulated acid secretion."( Effects of a gastric antisecretory-cytoprotectant 2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile (Sch 28 080) on cysteamine, reserpine and stress ulcers in rats.
Barnett, A; Brown, AD; Chiu, PJ; Gerhart, C, 1984
)
0.72
" Among three dosage regimens, the dosage of 50 mg/kg/day is effective as judged by the leucocyte cystine content, even if given in only three doses per day."( Treatment of cystinosis with cysteamine. A pilot study determining dose and form of application.
Bergonzi, E; Bühlmann, C; Herren, A; Lavanchy, P; Lüthy, C; Oetliker, O; Wyss, SR, 1981
)
0.55
" Adverse reactions were noted in 3 patients early in the study when a rapidly increasing dosage schedule was followed."( Adverse reactions to oral cysteamine use in nephropathic cystinosis.
Corden, BJ; Schneider, JA; Schulman, JD; Thoene, JG, 1981
)
0.56
" Repeated injections of pentagastrin in a dosage inducing an acid response equivalent to the one induced by cysteamine did not produce any histologic changes in Brunner's glands or any ulcerations."( Brunner's glands of the rat during cysteamine ulceration.
Christiansen, J; Kirkegaard, P; Poulsen, SS; Skov Olsen, P, 1981
)
0.75
" The maximum clastogenic activity of bleomycin in the presence of cysteamine was more than 10-fold greater than that of the same dosage of bleomycin alone."( Enhancement of the activity of bleomycin by cysteamine in a micronucleus assay in G0 human lymphocytes.
Hoffmann, GR; Littlefield, LG, 1995
)
0.79
" The compound facilitated penile erection in naive rats, and it ameliorated scopolamine-induced amnesia of rats in passive avoidance tasks with bell-shaped dose-response curves, while it dose-dependently reduced body weight gain in Zucker fatty rats."( A screening concept based on a hypothesis led to the development of a putative cognitive enhancer that stimulates penile erection.
Arakawa, H; Maeda, N; Matsuoka, N; Ohkubo, Y; Yamaguchi, I; Yamazaki, M, 1994
)
0.29
" Estrogen-primed rats were used in dose-response and time-course studies with CSH."( Characterization of cysteamine induction of the 22K prolactin variant in the rat pituitary.
Anthony, PK; Powers, CA, 1993
)
0.61
" Decreased responsiveness at high benzoate dosage indicates that the availability of coenzyme A is another factor that also limits the capacity of glycine conjugation."( Dependence of glycine conjugation on availability of glycine: role of the glycine cleavage system.
Fekete, T; Gregus, Z; Klaassen, CD; Varga, F, 1993
)
0.29
" Baseline GH concentrations were elevated in wethers dosed with 50 mg/kg BW CSH on day 3, whereas wethers dosed with 100 mg/kg BW CSH had lower baseline GH concentrations on day 0 (CSH x day interaction, P = ."( Effects of cysteamine on pulsatile growth hormone release and plasma insulin concentrations in sheep.
Harmon, DL; Hileman, SM; McLeod, KR; Mitchell, GE; Schillo, KK, 1995
)
0.68
") induced penile erection in rats, with bell-shaped dose-response curves."( Brain somatostatin depletion by cysteamine attenuates the penile erection induced by serotonergic and dopaminergic, but not by cholinergic, activation in rats.
Maeda, N; Matsuoka, N; Yamaguchi, I; Yamazaki, M, 1996
)
0.58
" However, at a gamma-ray dosage of 400 Gy, only a broad background, attributed to heterogeneously and multiply damaged oligonucleotide fragments with overlapping and varying electrophoretic mobilities, can be distinguished."( Single-strand breaks in oligodeoxyribonucleotides induced by fission neutrons and gamma radiation and measured by gel electrophoresis: protective effects of aminothiols.
Geacintov, NE; Li, B; Mao, B; Swenberg, CE; Tsao, H; Vaishnav, YN, 1997
)
0.3
") at a dosage of 300 or 450 mg/kg of body weight or subcutaneously (s."( Role of cytoprotectants and nitric oxide inhibition in nonsteroidal anti-inflammatory drug-induced gastroduodenal injury in the rat.
Albassam, MA; Lillie, LE; Macallum, GE; Percy, DH; Turner, PV, 2000
)
0.31
" It was found that the dose-effect curve based on the survival parameters of irradiated animals had two-phase character for cystamin and heparin with maxima of efficiency in the field of low and standard dosage of radioprotectors."( [Comparative study of the radiation-protective effectiveness of low doses of cysteamine, heparin, and naphtizine in experiments on mice].
Grebeniuk, AN; Lukashin, BP,
)
0.36
"The results of this study establish that cysteamine is rapidly cleared from the plasma but that an every 6 h dosing interval adequately maintains white blood cell cystine content below the target of 1 nmol cystine per mg protein."( Steady-state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in paediatric nephropathic cystinosis patients.
Belldina, EB; Brundage, RC; Huang, MY; Schneider, JA; Tracy, TS, 2003
)
0.83
" A formulation of cysteamine requiring less frequent dosing may improve compliance and possibly patient outcome."( Twice-daily cysteamine bitartrate therapy for children with cystinosis.
Barshop, BA; Dohil, R; Fidler, M; Gangoiti, JA; Kaskel, F; Schneider, JA, 2010
)
1.07
" Using a mouse model of infection with Plasmodium chabaudi AS, we observe that Cys dosing used to treat cystinosis in humans can strongly potentiate (by 3- to 4-fold) the antimalarial properties of the artemisinin derivatives artesunate and dihydroartemisinin."( Cysteamine, the molecule used to treat cystinosis, potentiates the antimalarial efficacy of artemisinin.
Fortin, A; Gros, P; Min-Oo, G; Poulin, JF, 2010
)
1.8
" Recent studies using cysteamine for for other diseases such as neurodegenerative disorders adopt the same dosing regimen for cysteamine."( Pharmacokinetics of enteric-coated cysteamine bitartrate in healthy adults: a pilot study.
Barshop, BA; Cabrera, BL; Dohil, R; Fidler, M; Gangoiti, JA; Schneider, JA, 2010
)
0.95
" However, cysteamine is associated with an offending odor and taste and this, coupled to a rapid first pass metabolism and a 6h dosing regimen, suggest a clear need to improve the therapy."( PEGylated derivatives of cystamine as enhanced treatments for nephropathic cystinosis.
Cairns, D; Di Salvo, A; Kay, G; Knott, RM; Omran, Z, 2011
)
0.77
" The diet was added CS at dosage of 100 mg/kg bw on the first day of the treated phase."( [Effects of cysteamine on the plasma levels of SS and some metabolic hormones in adult geese].
Ai, XJ; Chen, WH; Han, ZK; Zheng, YL, 2004
)
0.7
" CS was added in the diet at the dosage of 100 mg/kg bw on the first day of treated phase."( [Effect of cysteamine on the pancreatic secretion and enzymatic activity in geese].
Ai, XJ; Han, ZK, 2002
)
0.7
" Cystagon efficacy requires strict lifelong dosing every 6 hours."( A randomized controlled crossover trial with delayed-release cysteamine bitartrate in nephropathic cystinosis: effectiveness on white blood cell cystine levels and comparison of safety.
Bagger, MJ; Cochat, P; Cornelissen, E; Deschênes, G; Gaillard, S; Greenbaum, LA; Grimm, P; Langman, CB; Matossian, D; Morin, D; Niaudet, P; Rioux, P; Sarwal, M, 2012
)
0.62
" A cysteamine/adiponectin multimer dose-response curve was created."( The effect of cysteamine bitartrate on adiponectin multimerization in non-alcoholic fatty liver disease and healthy subjects.
Cabrera, BL; Dohil, R; Lavine, JE; Meyer, L; Phillips, SA; Schmeltzer, S, 2012
)
1.36
" However, due to its significant side effects and a strict 6-hourly dosing regimen, non-adherence to the immediate release of cysteamine bitartrate formulation (Cystagon®) is a major issue that might affect long-term outcome."( Cystinosis: a new perspective.
Besouw, MT; Casteels, I; Dyck, MV; Levtchenko, EN; Pinxten, AM; Veys, KR, 2016
)
0.64
"Cysteamine treatment should be started as early as possible, and dosage should be monitored and adapted based on trough WBC cystine levels."( Management dilemmas in pediatric nephrology: Cystinosis.
Besouw, MT; Cassiman, D; Claes, KJ; Levtchenko, EN; Van Dyck, M, 2015
)
1.86
"Understanding the phase behavior of pharmaceuticals is important for dosage form development and regulatory requirements, in particular after the incident with ritonavir."( An Integrated View of the Influence of Temperature, Pressure, and Humidity on the Stability of Trimorphic Cysteamine Hydrochloride.
Barrio, M; Do, B; Gana, I; Ghaddar, C; Nicolaï, B; Rietveld, IB; Safta, F; Tamarit, JL, 2015
)
0.63
" No abnormal alterations were observed in normal rats treated with HAEPD at the dosage studied."( Effect of Pithecellobium dulce (Roxb.) Benth. fruit extract on cysteamine induced duodenal ulcer in rats.
Geetha, A; Megala, J, 2015
)
0.66
" Plasma cysteamine concentrations were measured 8 h after dosing when reviewed at 1, 2 and 3 weeks and 6 h after dosing when reviewed at 5 weeks."( An Open-Label Investigation of the Pharmacokinetics and Tolerability of Oral Cysteamine in Adults with Cystic Fibrosis.
Chrystyn, H; Cotton, S; Devereux, G; Devlin, E; Fraser-Pitt, D; Griffiths, K; Norrie, J; O'Neil, D; Steele, S, 2016
)
1.1
" The established cysteamine formulation requires a strict dosing regimen at 6-h intervals."( Switching from immediate- to extended-release cysteamine in nephropathic cystinosis patients: a retrospective real-life single-center study.
Ahlenstiel-Grunow, T; Drube, J; Froede, K; Kanzelmeyer, NK; Kreuzer, M; Lerch, C; Pape, L, 2017
)
1.05
" We have introduced the cysteamine in two types of previously developed ocular hydrogels (ion sensitive hydrogel with the polymers gellan gum and kappa-carrageenan and another one composed of hyaluronic acid), aiming at increasing the ocular retention in order to extend the dosing interval."( Cysteamine polysaccharide hydrogels: Study of extended ocular delivery and biopermanence time by PET imaging.
Blanco-Mendez, J; Díaz-Tomé, V; Fernández-Ferreiro, A; García-Mazás, C; Gil-Martínez, M; González-Barcia, M; Herranz, M; Lamas, MJ; Luaces-Rodríguez, A; Otero-Espinar, FJ; Rodríguez-Ares, MT; Silva-Rodríguez, J, 2017
)
2.2
" Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine."( Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial.
Bourke, SJ; Daines, CL; Devereux, G; Doe, S; Dougherty, R; Franco, R; Fraser-Pitt, DJ; Innes, A; Kopp, BT; Lascano, J; Layish, D; Lovie, E; Lucidi, V; MacGregor, G; Murray, L; O'Neil, DA; Peckham, D; Robertson, J; Wrolstad, D, 2020
)
1.26
" The strict dosing regimen and poor stability are inconvenient and add to the burden of therapy."( A sustained release cysteamine microsphere/thermoresponsive gel eyedrop for corneal cystinosis improves drug stability.
Fedorchak, MV; Jimenez, J; Nischal, KK; Resnick, JL; Washington, MA, 2021
)
0.94
" This study investigated the pharmacokinetics, safety and tolerability of a new sustained-release cysteamine dosage form, PO-001, in healthy volunteers."( A novel sustained-release cysteamine bitartrate formulation for the treatment of cystinosis: Pharmacokinetics and safety in healthy male volunteers.
Berends, CL; Bergmann, KR; Büller, H; Burggraaf, J; de Leede, LGJ; de Loos, F; de Visser, SJ; de Vries, WS; Kamerling, IMC; Klarenbeek, NB; Moerland, M; Pagan, L; van der Wel, V; van Esdonk, MJ; Waals, H, 2021
)
1.14
" Our data show that DR-cysteamine should be dosed higher than 70% of the equivalent dose of IR-cysteamine in order to decrease cystine levels over an extended period of time."( A comparison of immediate release and delayed release cysteamine in 17 patients with nephropathic cystinosis.
Grebe, J; Grüneberg, M; Harms, E; Klank, S; Marquardt, T; Ottolenghi, C; Reunert, J; van Stein, C, 2021
)
1.18
" The priority of the Cys reaction with different α-dicarbonyls and its dependence on the Cys dosage were investigated."( Formation Priority of Pyrazines and 2-Acetylthiazole Dependent on the Added Cysteine and Fragments of Deoxyosones during the Thermal Process of the Glycine-Ribose Amadori Compound.
Hayat, K; Ho, CT; Liu, M; Xu, H; Yu, J; Zhang, X; Zhou, T, 2022
)
0.72
"The aim of this letter to the editor is to summarize the results from three clinical trial programs evaluating delayed-release cysteamine bitartrate (DR-CYS), which demonstrated the long-term clinical benefits in patients with nephropathic cystinosis when dosed every 12 h."( Long-term clinical benefits of delayed-release cysteamine bitartrate capsules in patients with nephropathic cystinosis (response to "A comparison of immediate release and delayed release cysteamine in 17 patients with nephropathic cystinosis").
Langman, CB, 2023
)
1.37
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (4)

RoleDescription
radiation protective agentAny compound that is able to protect normal cells from the damage caused by radiation therapy.
human metaboliteAny mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
mouse metaboliteAny mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
geroprotectorAny compound that supports healthy aging, slows the biological aging process, or extends lifespan.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (2)

ClassDescription
thiolAn organosulfur compound in which a thiol group, -SH, is attached to a carbon atom of any aliphatic or aromatic moiety.
amineA compound formally derived from ammonia by replacing one, two or three hydrogen atoms by hydrocarbyl groups.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (2)

PathwayProteinsCompounds
Pantothenate and CoA Biosynthesis619
Taurine and Hypotaurine Metabolism59

Protein Targets (28)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
thioredoxin reductaseRattus norvegicus (Norway rat)Potency12.53410.100020.879379.4328AID488772; AID488773; AID588453; AID588456
TDP1 proteinHomo sapiens (human)Potency29.85540.000811.382244.6684AID686978
thyroid stimulating hormone receptorHomo sapiens (human)Potency39.81070.001318.074339.8107AID926
regulator of G-protein signaling 4Homo sapiens (human)Potency7.51930.531815.435837.6858AID504845
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency14.12540.035520.977089.1251AID504332
vitamin D3 receptor isoform VDRAHomo sapiens (human)Potency19.95260.354828.065989.1251AID504847
chromobox protein homolog 1Homo sapiens (human)Potency50.11870.006026.168889.1251AID488953
cytochrome P450 3A4 isoform 1Homo sapiens (human)Potency1.00000.031610.279239.8107AID884; AID885
Gamma-aminobutyric acid receptor subunit piRattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-1Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit deltaRattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-5Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-3Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-1Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-2Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-4Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-3Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-6Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-3Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
GABA theta subunitRattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit epsilonRattus norvegicus (Norway rat)Potency1.00001.000012.224831.6228AID885
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Bile salt export pumpHomo sapiens (human)IC50 (µMol)331.00000.11007.190310.0000AID1449628
Histone-lysine N-methyltransferase EHMT2Homo sapiens (human)IC50 (µMol)100.00000.00251.14809.2000AID1374899
Glutaminyl-peptide cyclotransferaseMus musculus (house mouse)Ki42.00006.40006.40006.4000AID1796111
Histone-lysine N-methyltransferase EHMT1Homo sapiens (human)IC50 (µMol)100.00000.01300.79954.9000AID1374900
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (47)

Processvia Protein(s)Taxonomy
fatty acid metabolic processBile salt export pumpHomo sapiens (human)
bile acid biosynthetic processBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processBile salt export pumpHomo sapiens (human)
xenobiotic transmembrane transportBile salt export pumpHomo sapiens (human)
response to oxidative stressBile salt export pumpHomo sapiens (human)
bile acid metabolic processBile salt export pumpHomo sapiens (human)
response to organic cyclic compoundBile salt export pumpHomo sapiens (human)
bile acid and bile salt transportBile salt export pumpHomo sapiens (human)
canalicular bile acid transportBile salt export pumpHomo sapiens (human)
protein ubiquitinationBile salt export pumpHomo sapiens (human)
regulation of fatty acid beta-oxidationBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transportBile salt export pumpHomo sapiens (human)
bile acid signaling pathwayBile salt export pumpHomo sapiens (human)
cholesterol homeostasisBile salt export pumpHomo sapiens (human)
response to estrogenBile salt export pumpHomo sapiens (human)
response to ethanolBile salt export pumpHomo sapiens (human)
xenobiotic export from cellBile salt export pumpHomo sapiens (human)
lipid homeostasisBile salt export pumpHomo sapiens (human)
phospholipid homeostasisBile salt export pumpHomo sapiens (human)
positive regulation of bile acid secretionBile salt export pumpHomo sapiens (human)
regulation of bile acid metabolic processBile salt export pumpHomo sapiens (human)
transmembrane transportBile salt export pumpHomo sapiens (human)
negative regulation of transcription by RNA polymerase IIHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
cellular response to starvationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
regulation of DNA replicationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
DNA methylation-dependent heterochromatin formationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
synaptonemal complex assemblyHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
spermatid developmentHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
long-term memoryHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
fertilizationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
peptidyl-lysine dimethylationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
regulation of protein modification processHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
organ growthHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
phenotypic switchingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
negative regulation of gene expression via chromosomal CpG island methylationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
response to ethanolHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
behavioral response to cocaineHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
oocyte developmentHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
neuron fate specificationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
response to fungicideHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
cellular response to cocaineHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
cellular response to xenobiotic stimulusHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
negative regulation of autophagosome assemblyHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
negative regulation of transcription by RNA polymerase IIHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
chromatin organizationHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
DNA methylation-dependent heterochromatin formationHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
peptidyl-lysine monomethylationHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
peptidyl-lysine dimethylationHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
negative regulation of DNA-templated transcriptionHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
regulation of embryonic developmentHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
response to fungicideHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
positive regulation of cold-induced thermogenesisHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
negative regulation of transcription by RNA polymerase IIHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (21)

Processvia Protein(s)Taxonomy
protein bindingBile salt export pumpHomo sapiens (human)
ATP bindingBile salt export pumpHomo sapiens (human)
ABC-type xenobiotic transporter activityBile salt export pumpHomo sapiens (human)
bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
canalicular bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transporter activityBile salt export pumpHomo sapiens (human)
ABC-type bile acid transporter activityBile salt export pumpHomo sapiens (human)
ATP hydrolysis activityBile salt export pumpHomo sapiens (human)
RNA polymerase II transcription regulatory region sequence-specific DNA bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
transcription corepressor bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
p53 bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
protein bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
zinc ion bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
protein-lysine N-methyltransferase activityHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
enzyme bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
histone H3K9 methyltransferase activityHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
histone H3K27 methyltransferase activityHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
C2H2 zinc finger domain bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
histone H3K56 methyltransferase activityHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
histone H3K9me2 methyltransferase activityHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
promoter-specific chromatin bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
transcription corepressor bindingHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
p53 bindingHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
protein bindingHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
methyltransferase activityHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
zinc ion bindingHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
protein-lysine N-methyltransferase activityHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
histone H3K9 methyltransferase activityHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
histone H3K27 methyltransferase activityHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
C2H2 zinc finger domain bindingHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
histone H3K9me2 methyltransferase activityHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (17)

Processvia Protein(s)Taxonomy
basolateral plasma membraneBile salt export pumpHomo sapiens (human)
Golgi membraneBile salt export pumpHomo sapiens (human)
endosomeBile salt export pumpHomo sapiens (human)
plasma membraneBile salt export pumpHomo sapiens (human)
cell surfaceBile salt export pumpHomo sapiens (human)
apical plasma membraneBile salt export pumpHomo sapiens (human)
intercellular canaliculusBile salt export pumpHomo sapiens (human)
intracellular canaliculusBile salt export pumpHomo sapiens (human)
recycling endosomeBile salt export pumpHomo sapiens (human)
recycling endosome membraneBile salt export pumpHomo sapiens (human)
extracellular exosomeBile salt export pumpHomo sapiens (human)
membraneBile salt export pumpHomo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)
nucleusHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
nucleoplasmHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
nuclear speckHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
chromatinHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
nucleusHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
nucleusHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
nucleoplasmHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
nuclear bodyHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
chromatinHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
nucleusHistone-lysine N-methyltransferase EHMT1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (111)

Assay IDTitleYearJournalArticle
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347045Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347059CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347410qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library2019Cellular signalling, 08, Volume: 60A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID1347057CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347405qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347050Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347151Optimization of GU AMC qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347049Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID504836Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation2002The Journal of biological chemistry, Apr-19, Volume: 277, Issue:16
Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID588378qHTS for Inhibitors of ATXN expression: Validation
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347058CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1374897Inhibition of wild type recombinant human histone lysine methyltransferase GLP (951 to 1235 residues) expressed in Escherichia coli Rosetta BL21 DE3 PlysS at 10 uM using ARTKQTARKSTGGKA as substrate preincubated for 5 mins followed by substrate/SAM additi2018Bioorganic & medicinal chemistry letters, 04-15, Volume: 28, Issue:7
Inhibition of histone lysine methyltransferases G9a and GLP by ejection of structural Zn(II).
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID45885Antiviral activity against HIV-1ADA in CEM-SS cells using monocyte/macrophage cultures1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS.
AID1433758Corrector activity at CFTR F508 deletion mutant in primary human BE cells assessed as induction of autophagy by measuring increase in beclin-1 level at 250 uM measured after 24 hrs by immunoblotting2017Journal of medicinal chemistry, 01-12, Volume: 60, Issue:1
Fatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID136114Percent survival at 2 hr time interval between administration (225 mg/kg, ip) and irradiation* in mice1983Journal of medicinal chemistry, Sep, Volume: 26, Issue:9
Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.
AID317227Depletion of lysosomal cystine in cystinotic fibroblasts GM00008 at 50 uM after 72 hrs2008Bioorganic & medicinal chemistry letters, Mar-01, Volume: 18, Issue:5
A potential new prodrug for the treatment of cystinosis: design, synthesis and in-vitro evaluation.
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID589519Cytotoxicity against human cystinotic Fibroblast at 50 uM for 72 hrs by Alamar blue assay2011Bioorganic & medicinal chemistry letters, Apr-15, Volume: 21, Issue:8
Folate pro-drug of cystamine as an enhanced treatment for nephropathic cystinosis.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID135984Percent survival at 1 hr time interval between administration (225mg/kg, ip) and irradiation* in mice1983Journal of medicinal chemistry, Sep, Volume: 26, Issue:9
Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID135982Percent survival at 15 min time interval between administration (225 mg/kg, ip) and irradiation* in mice1983Journal of medicinal chemistry, Sep, Volume: 26, Issue:9
Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.
AID1365824Anti-inflammatory activity in Balb/C mouse assessed as reduction in carrageenan-induced hind paw oedema at 0.15 mmol/kg, ip pretreated for 1 hr followed by carrageenan challenge2017Bioorganic & medicinal chemistry letters, 11-01, Volume: 27, Issue:21
Dual antioxidant structures with potent anti-inflammatory, hypolipidemic and cytoprotective properties.
AID284868Mortality rate in Fischer 344 rat at 1.6 mmol/kg, sc after 4 days2007Bioorganic & medicinal chemistry, Jan-15, Volume: 15, Issue:2
Design and study of some novel ibuprofen derivatives with potential nootropic and neuroprotective properties.
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID552756Antinephropathic cystinosis activity in human cystinotic fibroblast assessed as decrease in cystine level at 50 uM after 24 hrs by Bradford reagent method2011Bioorganic & medicinal chemistry letters, Jan-01, Volume: 21, Issue:1
PEGylated derivatives of cystamine as enhanced treatments for nephropathic cystinosis.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID610690Cytotoxicity against cystinotic human fibroblasts at 50 uM after 72 hrs by Alamar blue assay2011Bioorganic & medicinal chemistry, Jun-01, Volume: 19, Issue:11
Synthesis and in vitro evaluation of novel pro-drugs for the treatment of nephropathic cystinosis.
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID251108Percentage of cleavage in single stranded peptide nucleic acid (PNA) DNA duplex was measured after treating with compound for 2 min; selectivity factor=1.5; PNA:DNA=5a:62005Bioorganic & medicinal chemistry letters, Feb-01, Volume: 15, Issue:3
Hybridization dependent cleavage of internally modified disulfide-peptide nucleic acids.
AID45374Antiviral activity against HIV-1 in CEM-SS cells using XXT assay1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS.
AID45376Antiviral activity against HIV-1ADA in CEM-SS cells using monocyte/macrophage cultures1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS.
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1399363Antioxidant activity assessed as rate of methyl radical scavenging activity by DMPO spin trap-based ESR spectrometric method2018Bioorganic & medicinal chemistry letters, 10-01, Volume: 28, Issue:18
Monoterpene's multiple free radical scavenging capacity as compared with the radioprotective agent cysteamine and amifostine.
AID1433760Corrector activity at CFTR F508 deletion mutant in primary human BE cells assessed as induction of autophagy by measuring decrease in p62 level at 250 uM measured after 24 hrs by immunoblotting2017Journal of medicinal chemistry, 01-12, Volume: 60, Issue:1
Fatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
AID260538Inhibition of lipid peroxidation of rat hepatic microsomal membrane lipids at 1 uM2006Bioorganic & medicinal chemistry letters, Feb-15, Volume: 16, Issue:4
Synthesis and pharmacochemical study of novel polyfunctional molecules combining anti-inflammatory, antioxidant, and hypocholesterolemic properties.
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1399361Antioxidant activity assessed as trolox equivalent of singlet oxygen scavenging activity by TMPD spin trap-based ESR spectrometric method2018Bioorganic & medicinal chemistry letters, 10-01, Volume: 28, Issue:18
Monoterpene's multiple free radical scavenging capacity as compared with the radioprotective agent cysteamine and amifostine.
AID161899Compound was tested for effects on HIV-1 protease; NI = No inhibition1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS.
AID284869Gastrointestinal toxicity in Fischer 344 rat assessed as gastrointestinal ulceration at 1.6 mmol/kg, sc after 4 days2007Bioorganic & medicinal chemistry, Jan-15, Volume: 15, Issue:2
Design and study of some novel ibuprofen derivatives with potential nootropic and neuroprotective properties.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID16783urine levels excreted after administration of cysteamine (175 mg/kg) to mice measured at 0-24 hr1983Journal of medicinal chemistry, Sep, Volume: 26, Issue:9
Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.
AID610691Reduction of intralysosomal cystine in cystinotic human fibroblasts at 50 uM after 24 hrs by Bradford method relative to control2011Bioorganic & medicinal chemistry, Jun-01, Volume: 19, Issue:11
Synthesis and in vitro evaluation of novel pro-drugs for the treatment of nephropathic cystinosis.
AID89002Compound was tested for binding of HIV-1 to CEM-ss cells; NI = No inhibition1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS.
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID1399357Antioxidant activity assessed as trolox equivalent of hydroxyl radical scavenging activity by DMPO spin trap-based ESR spectrometric method2018Bioorganic & medicinal chemistry letters, 10-01, Volume: 28, Issue:18
Monoterpene's multiple free radical scavenging capacity as compared with the radioprotective agent cysteamine and amifostine.
AID1374900Inhibition of wild type recombinant human histone lysine methyltransferase GLP (951 to 1235 residues) expressed in Escherichia coli Rosetta BL21 DE3 PlysS using ARTKQTARKSTGGKA as substrate preincubated for 5 mins followed by substrate/SAM addition measur2018Bioorganic & medicinal chemistry letters, 04-15, Volume: 28, Issue:7
Inhibition of histone lysine methyltransferases G9a and GLP by ejection of structural Zn(II).
AID1374902Inhibition of wild type recombinant human histone lysine methyltransferase GLP (951 to 1235 residues) expressed in Escherichia coli Rosetta BL21 DE3 PlysS assessed as zinc ions ejection from Cys4-Zn finger at 100 uM by FluoZin-3 based fluorescence assay2018Bioorganic & medicinal chemistry letters, 04-15, Volume: 28, Issue:7
Inhibition of histone lysine methyltransferases G9a and GLP by ejection of structural Zn(II).
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID284870Body weight change per 100g in Fischer 344 rat at 1.6 mmol/kg, sc after 4 days2007Bioorganic & medicinal chemistry, Jan-15, Volume: 15, Issue:2
Design and study of some novel ibuprofen derivatives with potential nootropic and neuroprotective properties.
AID1399360Antioxidant activity assessed as trolox equivalent of superoxide radical scavenging activity by CYPMPO spin trap-based ESR spectrometric method2018Bioorganic & medicinal chemistry letters, 10-01, Volume: 28, Issue:18
Monoterpene's multiple free radical scavenging capacity as compared with the radioprotective agent cysteamine and amifostine.
AID1399359Antioxidant activity assessed as trolox equivalent of tert-butyl peroxyl radical scavenging activity by CYPMPO spin trap-based ESR spectrometric method2018Bioorganic & medicinal chemistry letters, 10-01, Volume: 28, Issue:18
Monoterpene's multiple free radical scavenging capacity as compared with the radioprotective agent cysteamine and amifostine.
AID1449628Inhibition of human BSEP expressed in baculovirus transfected fall armyworm Sf21 cell membranes vesicles assessed as reduction in ATP-dependent [3H]-taurocholate transport into vesicles incubated for 5 mins by Topcount based rapid filtration method2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.
AID1374895Inhibition of wild type recombinant human histone lysine methyltransferase G9a (913 to 1193 residues) expressed in Escherichia coli Rosetta BL21 DE3 PlysS at 10 uM using ARTKQTARKSTGGKA as substrate preincubated for 5 mins followed by substrate/SAM additi2018Bioorganic & medicinal chemistry letters, 04-15, Volume: 28, Issue:7
Inhibition of histone lysine methyltransferases G9a and GLP by ejection of structural Zn(II).
AID200145Compound was tested for the effect on HIV-1 Reverse Transcriptase; NI = No inhibition1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS.
AID552755Cytotoxicity against human cystinotic fibroblast at 50 uM after 72 hrs by alamar blue assay2011Bioorganic & medicinal chemistry letters, Jan-01, Volume: 21, Issue:1
PEGylated derivatives of cystamine as enhanced treatments for nephropathic cystinosis.
AID1433792Corrector activity at CFTR F508 deletion mutant in primary human BE cells assessed as induction of autophagy by measuring decrease in p62 level at 250 uM measured after 24 hrs in presence of DHA by immunoblotting2017Journal of medicinal chemistry, 01-12, Volume: 60, Issue:1
Fatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
AID45884Antiviral activity against HIV-1 in CEM-SS cells using XXT assay1997Journal of medicinal chemistry, Jun-20, Volume: 40, Issue:13
Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS.
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1433759Corrector activity at CFTR F508 deletion mutant in primary human BE cells assessed as induction of autophagy by measuring increase in LC3-2 to LC3-1 ratio at 250 uM measured after 24 hrs by immunoblotting2017Journal of medicinal chemistry, 01-12, Volume: 60, Issue:1
Fatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID251090Percentage of cleavage in single stranded peptide nucleic acid was measured after treating with compound for 2 min; selectivity factor=1.5; PNA:DNA=5a:62005Bioorganic & medicinal chemistry letters, Feb-01, Volume: 15, Issue:3
Hybridization dependent cleavage of internally modified disulfide-peptide nucleic acids.
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID158688Inhibitory activity against Plasmodium falciparum1997Journal of medicinal chemistry, Oct-24, Volume: 40, Issue:22
Antimalarial activity of molecules interfering with Plasmodium falciparum phospholipid metabolism. Structure-activity relationship analysis.
AID1399358Antioxidant activity assessed as trolox equivalent of alkoxyl radical scavenging activity by DMPO spin trap-based ESR spectrometric method2018Bioorganic & medicinal chemistry letters, 10-01, Volume: 28, Issue:18
Monoterpene's multiple free radical scavenging capacity as compared with the radioprotective agent cysteamine and amifostine.
AID386623Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells at 100 uM by confocal microscopy2008Journal of medicinal chemistry, Oct-09, Volume: 51, Issue:19
Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1.
AID588220Literature-mined public compounds from Kruhlak et al phospholipidosis modelling dataset2008Toxicology mechanisms and methods, , Volume: 18, Issue:2-3
Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1433791Corrector activity at CFTR F508 deletion mutant in primary human BE cells assessed as induction of autophagy by measuring increase in LC3-2 to LC3-1 ratio at 250 uM measured after 24 hrs in presence of DHA by immunoblotting2017Journal of medicinal chemistry, 01-12, Volume: 60, Issue:1
Fatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
AID1374901Inhibition of wild type recombinant human histone lysine methyltransferase G9a (913 to 1193 residues) expressed in Escherichia coli Rosetta BL21 DE3 PlysS assessed as zinc ions ejection from Cys4-Zn finger at 100 uM by FluoZin-3 based fluorescence assay2018Bioorganic & medicinal chemistry letters, 04-15, Volume: 28, Issue:7
Inhibition of histone lysine methyltransferases G9a and GLP by ejection of structural Zn(II).
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID16770faecal levels excreted after administration of cysteamine (175 mg/kg) to mice measured at 0-30h1983Journal of medicinal chemistry, Sep, Volume: 26, Issue:9
Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID16785urine levels excreted after administration of cysteamine (175 mg/kg) to mice measured at 24-30 hr1983Journal of medicinal chemistry, Sep, Volume: 26, Issue:9
Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID106125Effect on intracellular GSH content at 250 uM in human macrophage-derived monocytes (MDMs)2001Bioorganic & medicinal chemistry letters, May-07, Volume: 11, Issue:9
NAC/MEA conjugate: a new potent antioxidant which increases the GSH level in various cell lines.
AID134599Lethal dose in mice1983Journal of medicinal chemistry, Sep, Volume: 26, Issue:9
Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.
AID1399362Antioxidant activity assessed as trolox equivalent of methyl radical scavenging activity by DMPO spin trap-based ESR spectrometric method2018Bioorganic & medicinal chemistry letters, 10-01, Volume: 28, Issue:18
Monoterpene's multiple free radical scavenging capacity as compared with the radioprotective agent cysteamine and amifostine.
AID1374899Inhibition of wild type recombinant human histone lysine methyltransferase G9a (913 to 1193 residues) expressed in Escherichia coli Rosetta BL21 DE3 PlysS using ARTKQTARKSTGGKA as substrate preincubated for 5 mins followed by substrate/SAM addition measur2018Bioorganic & medicinal chemistry letters, 04-15, Volume: 28, Issue:7
Inhibition of histone lysine methyltransferases G9a and GLP by ejection of structural Zn(II).
AID1433790Corrector activity at CFTR F508 deletion mutant in primary human BE cells assessed as induction of autophagy by measuring increase in beclin-1 level at 250 uM in presence of DHA measured after 24 hrs by immunoblotting2017Journal of medicinal chemistry, 01-12, Volume: 60, Issue:1
Fatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
AID16784urine levels excreted after administration of cysteamine (175 mg/kg) to mice measured at 0-6 hr1983Journal of medicinal chemistry, Sep, Volume: 26, Issue:9
Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
AID1796111QC Inhibition Testing from Article 10.1021/bi051142e: \\Isolation, catalytic properties, and competitive inhibitors of the zinc-dependent murine glutaminyl cyclase.\\2005Biochemistry, Oct-11, Volume: 44, Issue:40
Isolation, catalytic properties, and competitive inhibitors of the zinc-dependent murine glutaminyl cyclase.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (3,083)

TimeframeStudies, This Drug (%)All Drugs %
pre-19901569 (50.89)18.7374
1990's431 (13.98)18.2507
2000's375 (12.16)29.6817
2010's528 (17.13)24.3611
2020's180 (5.84)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 37.66

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index37.66 (24.57)
Research Supply Index8.12 (2.92)
Research Growth Index4.54 (4.65)
Search Engine Demand Index111.66 (26.88)
Search Engine Supply Index3.67 (0.95)

This Compound (37.66)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials60 (1.81%)5.53%
Reviews115 (3.48%)6.00%
Case Studies85 (2.57%)4.05%
Observational1 (0.03%)0.25%
Other3,046 (92.11%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (32)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Multi-center, Randomized, Double-blind, Placebo-controlled, Study to Assess the Safety, Tolerability, Pharmacodynamics (PD) and Efficacy of TTI-0102 for the Treatment of Patients With Mild to Moderate COVID-19 [NCT05212662]Phase 260 participants (Anticipated)Interventional2024-06-30Not yet recruiting
Efficacy and Safety of Topical Cysteamine for Postinflammatory Hyperpigmentation: A Randomized Control, Double Blinded-trial [NCT05206318]40 participants (Anticipated)Interventional2021-12-10Recruiting
A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study Investigating the Optimal Dose Regimen, Efficacy, and Safety of Adding Oral Cysteamine in Adult Patients Being Treated for an Exacerbation of CF-associated Lung Disease [NCT03000348]Phase 291 participants (Actual)Interventional2016-12-31Completed
Cysteamine for Asthma [NCT03883984]Phase 160 participants (Actual)Interventional2019-06-18Completed
Multicentre, Ambispective, Observational, Real Life Study to Assess the Quality of Life Effectiveness of Extended Release (ER) Oral Cysteamine Therapy (Procysbi) in Belgian Patients Suffering From Nephropathic Cystinosis [NCT04246060]31 participants (Anticipated)Observational2020-07-31Enrolling by invitation
Combination Topical Cysteamine and Fractional 1927nm Low-Powered Diode Laser [NCT05656833]20 participants (Anticipated)Interventional2022-10-28Recruiting
A Randomized, Crossover Pharmacokinetic and Pharmacodynamic Study to Determine the Safety and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103), Compared to Cystagon® in Patients With Nephropathic Cystinosis [NCT01000961]Phase 343 participants (Actual)Interventional2010-06-30Completed
Compare the Efficacy and Safety Profile of Cysteamine and Hydroquinone in Melasma as Topical Application [NCT05969587]Phase 328 participants (Actual)Interventional2019-11-28Completed
Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia [NCT02735707]Phase 310,000 participants (Anticipated)Interventional2016-04-11Recruiting
A Cohort of Patients With Cystinosis : Compliance to Cysteamine and Neurological Complications [NCT02012114]65 participants (Actual)Interventional2011-12-31Completed
[NCT02766855]26 participants (Actual)Interventional2004-01-31Completed
Trial of Topical Cysteamine in the Treatment of Corneal Cystine Crystal Accumulation in Cystinosis [NCT00001213]Phase 2328 participants (Actual)Interventional1986-04-30Completed
[NCT00010426]30 participants Interventional1999-12-31Completed
An Open Trial of Cysteamine Treatment in Schizophrenia [NCT01139125]3 participants (Actual)Interventional2009-09-30Terminated(stopped due to The study was stopped after 4 years of recruitment difficulties.)
An Open Label Investigation of the Tolerability and Pharmacokinetics of Oral Cysteamine in Adults With Cystic Fibrosis. [NCT02212431]Phase 1/Phase 210 participants (Actual)Interventional2014-08-31Completed
A Long-Term, Open-Label, Safety and Efficacy Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Patients With Cystinosis [NCT01197378]Phase 360 participants (Actual)Interventional2010-08-27Completed
An Open-Label Study of Cysteamine Bitartrate in Treatment-Resistant Major Depression [NCT00715559]3 participants (Actual)Interventional2008-07-31Terminated(stopped due to Change in resources available for study procedures.)
Use of Cysteamine in the Treatment of Cystinosis [NCT00359684]330 participants (Anticipated)Observational1979-01-04Recruiting
[NCT00799578]Phase 1/Phase 213 participants (Actual)Interventional2008-10-31Completed
Safety and Efficacy Trial of a Proposed NDA Formulation of Topical Cysteamine in the Treatment of Corneal Cystine Crystal Accumulation in Cystinosis [NCT00001736]Phase 151 participants Interventional1998-05-31Completed
A Pilot Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Cysteamine Bitartrate Delayed-release Capsules (RP103), Compared to Cysteamine Bitartrate (Cystagon®) in Patients With Nephropathic Cystinosis [NCT00872729]Phase 1/Phase 29 participants (Actual)Interventional2009-05-31Completed
An Open-Label, Safety and Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naïve Patients With Cystinosis [NCT01744782]Phase 317 participants (Actual)Interventional2012-12-20Completed
A Phase II/III Study of Cysteamine (Mercaptoethylamine) and Zidovudine for the Treatment of HIV Disease [NCT00002110]Phase 2300 participants InterventionalCompleted
A Combination Therapy With Cystagon and N-Acetylcysteine for INCL Patients [NCT00028262]Phase 410 participants (Actual)Interventional2001-02-28Completed
Food-Effect on Bioavailability of Cystagon™ in Normal, Healthy Adults [NCT01432561]8 participants (Actual)Interventional2011-09-30Completed
An Open-Label, Dose-Escalating Study to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of Cysteamine Bitartrate Delayed-release Capsules (RP103) for Treatment of Children With Inherited Mitochondrial Disease [NCT02023866]Phase 236 participants (Actual)Interventional2014-05-31Completed
Open-label, Single-arm, Multicenter Study to Assess the Safety of Cystadrops® in Pediatric Cystinosis Patients From 6 Months to Less Than 2 Years Old [NCT04125927]Phase 35 participants (Actual)Interventional2020-09-01Completed
An Open-label Study Evaluating the Safety, Antiviral Activity, and Pharmacokinetics of IMC-I109V in HLA-A*02:01 Positive Participants With Chronic HBV Infection Who Are Non-Cirrhotic, Hepatitis B e Antigen-negative, and Virally Suppressed [NCT05867056]Phase 1108 participants (Anticipated)Interventional2020-08-12Recruiting
A Long-Term, Open-Label, Safety, Tolerability and Superior Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Patients With Cystinosis [NCT01733316]Phase 341 participants (Actual)Interventional2013-01-31Completed
Cysteamine Bitartrate Delayed-Release for the Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in Children (CyNCh) [NCT01529268]Phase 2/Phase 3169 participants (Actual)Interventional2012-06-30Completed
A Phase 1/2 Pharmacokinetic and Pharmacodynamic Study of NPI-001 Oral Solution Compared to Cysteamine Bitartrate in Cystinosis Patients [NCT05994534]Phase 1/Phase 212 participants (Anticipated)Interventional2023-10-29Recruiting
A Long-Term Open-Label Extension Study of RP103-MITO-001 to Assess the Safety, Tolerability and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103) for Treatment of Children With Inherited Mitochondrial Disease [NCT02473445]Phase 222 participants (Actual)Interventional2015-05-19Terminated(stopped due to Sponsor decision to end development of RP103 for mitochondrial disease due to lack of efficacy demonstrated in base study RP103-MITO-001.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00001213 (2) [back to overview]Number of Eyes With a Corneal Cystine Crystal Score (CCCS) Response
NCT00001213 (2) [back to overview]Number of Participants With Serious and Non-Serious Adverse Events
NCT00028262 (1) [back to overview]Change in Cellular Granular Osmiophilic Deposits (GRODs) in Electron Micrographs of Peripheral White Blood Cells.
NCT00715559 (4) [back to overview]Clinical Global Impression Scales for Severity (CGI-S) and Improvement (CGI-I)
NCT00715559 (4) [back to overview]Montgomery-Åsberg Depression Rating Scale (MADRS)
NCT00715559 (4) [back to overview]Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16)
NCT00715559 (4) [back to overview]Systematic Assessment for Treatment Emergent Effects (SAFTEE)
NCT00799578 (1) [back to overview]Normalization or >50% of Serum ALT Levels From Baseline
NCT00872729 (4) [back to overview]Pharmacodynamic Parameter: Changes of White Blood Cell (WBC) Cystine Level From Baseline
NCT00872729 (4) [back to overview]Plasma Pharmacokinetic Parameter: AUC(0-t) of Cysteamine
NCT00872729 (4) [back to overview]Plasma Pharmacokinetic Parameter: Cmax of Cysteamine
NCT00872729 (4) [back to overview]Plasma Pharmacokinetic Parameter: Tmax of Cysteamine
NCT01000961 (4) [back to overview]Comparison of Cysteamine PK Profiles, AUC(0-t), Between RP103 and Cystagon®.
NCT01000961 (4) [back to overview]Comparison of Cysteamine PK Profiles, Steady State Cmax, Between RP103 and Cystagon®.
NCT01000961 (4) [back to overview]Comparison of Cysteamine PK Profiles, Steady State Tmax, Between RP103 and Cystagon®.
NCT01000961 (4) [back to overview]The Steady-state White Blood Cell Cystine Levels of RP103 Compared to Cystagon®
NCT01197378 (3) [back to overview]Number of Participants With Treatment-emergent Adverse Events
NCT01197378 (3) [back to overview]White Blood Cell Cystine Concentration
NCT01197378 (3) [back to overview]Trough Plasma Cysteamine Concentration
NCT01432561 (3) [back to overview]Cysteamine Absorption: Area Under the Plasma Concentration Curve (AUC)
NCT01432561 (3) [back to overview]Peak Plasma Cysteamine Concentration (Cmax)
NCT01432561 (3) [back to overview]Time to Peak Plasma Cysteamine Concentration (Tmax)
NCT01529268 (25) [back to overview]Change in HOMA-IR
NCT01529268 (25) [back to overview]Hepatocellular Ballooning: Patients With Improvement
NCT01529268 (25) [back to overview]Portal Inflammation: Patients With Improvement
NCT01529268 (25) [back to overview]Portal Inflammation: Change in Score
NCT01529268 (25) [back to overview]Lobular Inflammation: Patients With Improvement
NCT01529268 (25) [back to overview]Lobular Inflammation: Change in Score
NCT01529268 (25) [back to overview]Hepatocellular Ballooning: Change in Score
NCT01529268 (25) [back to overview]Fibrosis: Patients With Improvement
NCT01529268 (25) [back to overview]Fibrosis: Change in Stage
NCT01529268 (25) [back to overview]Change in Weight (kg)
NCT01529268 (25) [back to overview]Change in Fasting Serum Glucose
NCT01529268 (25) [back to overview]Change in Fasting Insulin
NCT01529268 (25) [back to overview]Change in Diastolic Blood Pressure
NCT01529268 (25) [back to overview]Change in Body-mass Index Z-score
NCT01529268 (25) [back to overview]Change in Body-mass Index
NCT01529268 (25) [back to overview]Improvement in Nonalcoholic Fatty Liver Disease (NAFLD)
NCT01529268 (25) [back to overview]Change in Waist Circumference
NCT01529268 (25) [back to overview]Change in Systolic Blood Pressure
NCT01529268 (25) [back to overview]Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)
NCT01529268 (25) [back to overview]Reduction in MRI-determined Hepatic Fat Fraction
NCT01529268 (25) [back to overview]Resolution of NASH
NCT01529268 (25) [back to overview]Steatosis: Change in Score
NCT01529268 (25) [back to overview]Steatosis: Patients With Improvement
NCT01529268 (25) [back to overview]Change in Pediatric Quality of Life Inventory (PedsQL) Score
NCT01529268 (25) [back to overview]Change in Serum Aminotransferase and Gamma-glutamyl Transpeptidase
NCT01733316 (6) [back to overview]Average Difference Between Morning and Non-Morning Log White Blood Cell (WBC) Cystine Values
NCT01733316 (6) [back to overview]Area Under the Plasma Concentration Time Curve From Time Point 0 Through the Last Measurable Point (AUC0-t) for Plasma Cysteamine
NCT01733316 (6) [back to overview]Halitosis Substudy: Expired Air DMS Concentrations
NCT01733316 (6) [back to overview]Halitosis Substudy: Maximum Plasma Concentration (Cmax) for Plasma Cysteamine
NCT01733316 (6) [back to overview]Halitosis Substudy: Time to Cmax (Tmax) for Plasma Cysteamine
NCT01733316 (6) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
NCT01744782 (5) [back to overview]Mean White Blood Cell (WBC) Cystine Concentration at Each Visit
NCT01744782 (5) [back to overview]Area Under the Plasma Concentration Versus Time Curve (AUC) of Cysteamine
NCT01744782 (5) [back to overview]Time of the Maximum Observed Plasma Concentration (Tmax) of Cysteamine
NCT01744782 (5) [back to overview]Number of Participants With Adverse Events
NCT01744782 (5) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Cysteamine
NCT02023866 (10) [back to overview]Change From Baseline in Friedreich Ataxia Rating Scale
NCT02023866 (10) [back to overview]Change From Baseline in Glutathione
NCT02023866 (10) [back to overview]Change From Baseline in Glutathione Disulfide
NCT02023866 (10) [back to overview]Change From Baseline in Gross Motor Function
NCT02023866 (10) [back to overview]Change From Baseline in Jamar Dynamometer Hand Strength
NCT02023866 (10) [back to overview]Change From Baseline in Lactic Acid
NCT02023866 (10) [back to overview]Change From Baseline in Modified Lansky Play Performance Scale
NCT02023866 (10) [back to overview]Change From Baseline in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Sections I-IV
NCT02023866 (10) [back to overview]Change From Baseline in 6 Minute Walk Test
NCT02023866 (10) [back to overview]Change From Baseline in Barry-Albright Dystonia Scale Total Score
NCT03000348 (14) [back to overview]Change From Baseline in Sputum Bacterial Load
NCT03000348 (14) [back to overview]Safety and Tolerability Assessed by the Number of Subjects With Adverse Events
NCT03000348 (14) [back to overview]Change From Baseline in Weight
NCT03000348 (14) [back to overview]Change From Baseline in Sputum IL8
NCT03000348 (14) [back to overview]Change From Baseline in Neutrophil Elastase Levels
NCT03000348 (14) [back to overview]Change From Baseline in Jarad and Sequeiros Symptom Score Questionnaire
NCT03000348 (14) [back to overview]Change From Baseline in FEV1
NCT03000348 (14) [back to overview]Change From Baseline in CFRSD-CRISS
NCT03000348 (14) [back to overview]Change From Baseline in CFQ-R
NCT03000348 (14) [back to overview]Assessment of Blood Cysteamine Levels
NCT03000348 (14) [back to overview]Change From Baseline in C-Reactive Protein
NCT03000348 (14) [back to overview]Change From Baseline in BMI
NCT03000348 (14) [back to overview]Change From Baseline in Blood Leukocyte Count
NCT03000348 (14) [back to overview]Assessment of Sputum Cysteamine Levels

Number of Eyes With a Corneal Cystine Crystal Score (CCCS) Response

"Response is defined as a decrease from baseline of at least 1 in Corneal Cystine Crystal Score (CCCS) at any time on study when baseline CCCS is greater than or equal to 1, or CCCS does not increase at least 1 at any time on study when baseline CCCS is less than 1.~The CCCS is based on a library of slit-lamp photographs of corneas with increasing crystal densities (0-3). Slit-lamp photos were to be taken to assess the extent of the corneal crystal accumulation. To minimize bias when assessing the extent of corneal crystal accumulation, photos were centrally graded at the National Eye Institute (NEI) where each photo was graded independently by masked graders. If more than one CCCS was recorded in a given study year, the highest (worst) CCCS value was used for that year.~The results were obtained from a combined analyses of the NIH cysteamine studies evaluating various cysteamine ophthalmic solution formulations from 1986 through 2005." (NCT00001213)
Timeframe: Any Time Point Up to 19 Years

Interventioneyes (Number)
Cysteamine Topical Solution98

[back to top]

Number of Participants With Serious and Non-Serious Adverse Events

Since efficacy of ophthalmic cysteamine was established and a New Drug Application (NDA) filed, the post-hoc primary outcome measure is the evaluation of safety information. There was no specified time frame for this outcome measure, as safety data was being collected until the drug became available for commercial purchase in May 2013. (NCT00001213)
Timeframe: Any Time Point up to 27 Years

Interventionparticipants (Number)
Cysteamine Topical Solution257

[back to top]

Change in Cellular Granular Osmiophilic Deposits (GRODs) in Electron Micrographs of Peripheral White Blood Cells.

The GRODs in peripheral white blood cells from all patients before and during treatment were analyzed by transmission electron microscopy (TEM) at 30000xmagnification. Two investigators working independently of each other identified and counted the GRODs and the results were averaged. (NCT00028262)
Timeframe: 10 years

InterventionAverage number of GRODs (Mean)
Drug Cystagon and N-acetylcysteine-0.3317

[back to top]

Clinical Global Impression Scales for Severity (CGI-S) and Improvement (CGI-I)

"This set of scales measures global improvement in a patient's level of symptoms, without reference to a particular condition (ie depression). GCI-S is a measure of severity, which ranges from 0 (not ill) to 7 (severely ill). CGI-I is a measure of change, with a score of 4 indicating no change, 1 indicating very much improved and 7 indicating very much worse." (NCT00715559)
Timeframe: 8 weeks

Interventionscale score (Mean)
Cysteamine Bitartrate4

[back to top]

Montgomery-Åsberg Depression Rating Scale (MADRS)

This scale measures depression severity. It ranges from a score of 0 to 60, with higher score indicating higher level of depression severity. (NCT00715559)
Timeframe: 8 weeks

Interventionscale score (Mean)
Cysteamine Bitartrate27

[back to top]

Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16)

This is a self-report which measures the level of depression severity. I ranges from 0 (no illness) to 27 (severe illness). (NCT00715559)
Timeframe: 8 weeks

Interventionscale score (Mean)
Cysteamine Bitartrate13.3

[back to top]

Systematic Assessment for Treatment Emergent Effects (SAFTEE)

"The SAFTEE is used to measure somatic and other symptoms which may arise during the course of a clinical trial. This is a non-quantitative instrument that does not yield a numeric score. Instead, it provides study subjects the opportunity to check off symptoms listed on a checklist and indicate if the severity of the symptoms is mild moderate or severe. The reported values represent symptoms that were indicated at any point during the 8 week trial at a level of moderate or severe that also represented a change from a baseline-line pre-intervention SAFTEE assessment." (NCT00715559)
Timeframe: weekly, for 8 weeks

Interventionsymptoms (Mean)
Cysteamine Bitartrate24.3

[back to top]

Normalization or >50% of Serum ALT Levels From Baseline

(NCT00799578)
Timeframe: 6 months

Interventionparticipants (Number)
Number of Improved Subjects7

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Pharmacodynamic Parameter: Changes of White Blood Cell (WBC) Cystine Level From Baseline

"The pharmacodynamic (PD) parameter measures the changes of WBC cystine level from the baseline.~Cystine is a disulfide amino acid formed through oxidation of two molecules of cysteine; hence, cystine's concentration is commonly given in half-cystine equivalents to avoid confusion.~The level of cystine in WBC/leukocytes is expressed in units of nmol half-cystine/mg protein (nmol ½ cystine/mg protein). Half-cystine is quantified by a reduction of cystine followed by an assay for cysteine, which is then normalized by the total cellular protein content within the sample using methods of such as Lowry assay, bicinchoninic acid assay, or Bradford." (NCT00872729)
Timeframe: up to 12 hours post Cystagon® dosing and RP103 dosing

Interventionnmol 1/2 cystine/mg protein (Mean)
Cystagon® (0.5 Hour)0.11
Cystagon® (1 Hour)-0.10
RP103 (1 Hour)0.87
Cystagon® (2 Hour)-0.07
RP103 (2.5 Hour)0.19
Cystagon® (3 Hour)-0.14
RP103 (3 Hour)0.43
Cystagon® (4 Hour)-0.01
RP103 (4 Hour)0.10
Cystagon® (6 Hour)0.30
RP103 (6 Hour)0.22
RP103 (8 Hour)0.20
RP103 (10 Hour)0.45
Cystagon® (12 Hour)0.37
RP103 (12 Hour)0.72

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Plasma Pharmacokinetic Parameter: AUC(0-t) of Cysteamine

t = 6 for Cystagon and t = 12 for RP103. Cystagon is dosed every 6 hours and there is no measurement after 6 hours and up to 12 hours. (NCT00872729)
Timeframe: 12 hours post RP103 dosing and 6 hours post 1st Cystagon® dosing

Interventionumol•h/L (Geometric Mean)
Cystagon®107.89
RP103119.17

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Plasma Pharmacokinetic Parameter: Cmax of Cysteamine

(NCT00872729)
Timeframe: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing

Interventionumol/L (Geometric Mean)
Cystagon®42.02
RP10333.06

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Plasma Pharmacokinetic Parameter: Tmax of Cysteamine

(NCT00872729)
Timeframe: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing

Interventionhour (Median)
Cystagon®1.00
RP1033.00

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Comparison of Cysteamine PK Profiles, AUC(0-t), Between RP103 and Cystagon®.

(NCT01000961)
Timeframe: 6 hours post dosing for Cystagon®; 12 hours post dosing for RP103.

InterventionAUC(0-t) (min*mg/L) (Least Squares Mean)
Cystagon®357
RP103739

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Comparison of Cysteamine PK Profiles, Steady State Cmax, Between RP103 and Cystagon®.

(NCT01000961)
Timeframe: 4 weeks after the last subject has completed the study

InterventionCmax (mg/L) (Least Squares Mean)
Cystagon®2.73
RP1033.70

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Comparison of Cysteamine PK Profiles, Steady State Tmax, Between RP103 and Cystagon®.

(NCT01000961)
Timeframe: 4 weeks after the last subject has completed the study

InterventionTmax (minute) (Least Squares Mean)
Cystagon®72
RP103187

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The Steady-state White Blood Cell Cystine Levels of RP103 Compared to Cystagon®

(NCT01000961)
Timeframe: 4 weeks after the last subject has completed the study

Interventionnmol ½ Cystine / mg protein (Least Squares Mean)
RP1030.5152
Cystagon®0.4367

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Number of Participants With Treatment-emergent Adverse Events

"Drug-related adverse events (AEs) are AEs the investigator assessed as having relation to drug of 'possibly', 'probably' or 'definitely'.~The severity of AEs was categorized according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 as follows:~Mild (Grade 1): experience is minor and does not cause significant discomfort to subject or change in activities of daily living (ADL); subject is aware of symptoms but symptoms are easily tolerated;~Moderate (Grade 2): experience is an inconvenience or concern to the subject and causes interference with ADL, but the subject is able to continue with ADL.~Severe (Grade 3): experience significantly interferes with ADL and the subject is incapacitated and/or unable to continue with ADL~Life-threatening (Grade 4): experience that, in the view of the Investigator, places the subject at immediate risk of death from the event as it occurred." (NCT01197378)
Timeframe: From first dose of study drug to 7 days after the last dose; median duration of treatment was 1461 days.

InterventionParticipants (Count of Participants)
Any adverse eventAdverse events related to study drugAdverse events ≥ Grade 3Serious adverse eventsAdverse events leading to discontinuation
Cysteamine Bitartrate583724323

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White Blood Cell Cystine Concentration

White blood cell (WBC) cystine concentration was determined using high performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). (NCT01197378)
Timeframe: Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose

Interventionnmol 1/2 Cystine/mg protein (Mean)
Day 1Month 6Year 1Year 1.5Year 2Year 3Year 4Year 5
Cysteamine Bitartrate1.680.930.650.750.650.661.381.17

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Trough Plasma Cysteamine Concentration

Plasma cysteamine concentration was determined using methods employing Hydrophilic Interaction Liquid Chromatography (HILC) high pressure liquid chromatography (HPLC) tandem mass spectrometry (HPLC-MS/MS). (NCT01197378)
Timeframe: Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose

Interventionmg/L (Mean)
Day 1Month 6Year 1Year 1.5Year 2Year 3Year 4Year 5
Cysteamine Bitartrate0.170.290.370.480.360.340.470.40

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Cysteamine Absorption: Area Under the Plasma Concentration Curve (AUC)

Subjects were randomized to one of two possible treatment sequences using block randomization: Sequence 1 - fasted, high-fat, high-protein or Sequence 2 - high-protein, high-fat, fasted. Sequence assignment determined the treatment condition corresponding to Period I, II & III visits. (NCT01432561)
Timeframe: 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180 minutes, and 3.5, 4, 4.5, 5, 6 hours post-dose

Interventionmin*uM (Mean)
FastedFed High-Fat/CalorieFed High-Protein
Cysteamine Bitartrate361827992457

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Peak Plasma Cysteamine Concentration (Cmax)

Subjects were randomized to one of two possible treatment sequences using block randomization: Sequence 1 - fasted, high-fat, high-protein or Sequence 2 - high-protein, high-fat, fasted. Sequence assignment determined the treatment condition corresponding to Period I, II & III visits. (NCT01432561)
Timeframe: 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180 minutes, and 3.5, 4, 4.5, 5, 6 hours post-dose

InterventionuM (Mean)
FastedFed High-Fat/CalorieFed High-Protein
Cysteamine Bitartrate26.322.417.2

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Time to Peak Plasma Cysteamine Concentration (Tmax)

Subjects were randomized to one of two possible treatment sequences using block randomization: Sequence 1 - fasted, high-fat, high-protein or Sequence 2 - high-protein, high-fat, fasted. Sequence assignment determined the treatment condition corresponding to Period I, II & III visits. (NCT01432561)
Timeframe: 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180 minutes, and 3.5, 4, 4.5, 5, 6 hours post-dose

Interventionminutes (Mean)
FastedFed High-Fat/CalorieFed High-Protein
Cysteamine Bitartrate71.2106.9120

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Change in HOMA-IR

(Glucose (mmol/L) x insulin (pmol/L))/22.5 (NCT01529268)
Timeframe: 52 weeks

Intervention(10E-15 mol^2)/L^2 (Mean)
DR Cysteamine Bitartrate Capsule1.4
DR Cysteamine Bitartrate Placebo3.6

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Hepatocellular Ballooning: Patients With Improvement

Improvement in hepatocellular ballooning defined as any decrease in hepatocellular ballooning score comparing 52-week biopsy to baseline. (NCT01529268)
Timeframe: 52 weeks

Interventionparticipants (Number)
DR Cysteamine Bitartrate Capsule17
DR Cysteamine Bitartrate Placebo21

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Portal Inflammation: Patients With Improvement

Improvement in portal inflammation defined as any decrease in portal inflammation score comparing 52-week biopsy to baseline. (NCT01529268)
Timeframe: 52 weeks

Interventionparticipants (Number)
DR Cysteamine Bitartrate Capsule18
DR Cysteamine Bitartrate Placebo14

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Portal Inflammation: Change in Score

Change from baseline in portal inflammation score. The amount of portal inflammation is based on central pathologist grading of liver biopsies: 0=none; 1=mild, 2=more than mild. Change in portal inflammation score has a possible range of -2 to +2, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement). (NCT01529268)
Timeframe: 52 weeks

Interventionunits on a scale (Mean)
DR Cysteamine Bitartrate Capsule-0.1
DR Cysteamine Bitartrate Placebo-0.1

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Lobular Inflammation: Patients With Improvement

Improvement in lobular inflammation defined as any decrease in lobular inflammation grade comparing 52-week biopsy to baseline. (NCT01529268)
Timeframe: 52 weeks

Interventionparticipants (Number)
DR Cysteamine Bitartrate Capsule32
DR Cysteamine Bitartrate Placebo17

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Lobular Inflammation: Change in Score

Change from baseline in lobular inflammation score. The amount of lobular inflammation is based on central pathologist grading of liver biopsies, and combines mononuclear, fat granulomas, and polymorphonuclear (pmn) foci: 0=none; 1=<2 under 20x magnification, 2=2-4 under 20x magnification, 3=>4 under 20x magnification. Change in lobular inflammation score has a possible range of -3 to +3, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement). (NCT01529268)
Timeframe: 52 weeks

Interventionunits on a scale (Mean)
DR Cysteamine Bitartrate Capsule-0.4
DR Cysteamine Bitartrate Placebo-0.1

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Hepatocellular Ballooning: Change in Score

Change from baseline in hepatocellular ballooning score. The amount of hepatocellular ballooning is based on central pathologist grading of liver biopsies: 0=none; 1=few ballooned hepatocytes, 2=many ballooned hepatocytes. Change in hepatocellular ballooning score has a possible range of -2 to +2, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement). (NCT01529268)
Timeframe: 52 weeks

Interventionunits on a scale (Mean)
DR Cysteamine Bitartrate Capsule-0.1
DR Cysteamine Bitartrate Placebo-0.3

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Fibrosis: Patients With Improvement

Improvement in fibrosis stage defined as any decrease in fibrosis stage comparing 52-week biopsy to baseline. (NCT01529268)
Timeframe: 52 weeks

Interventionparticipants (Number)
DR Cysteamine Bitartrate Capsule25
DR Cysteamine Bitartrate Placebo23

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Fibrosis: Change in Stage

Change from baseline in fibrosis stage. The amount of fibrosis is based on central pathologist grading of liver biopsies: 0=none; 1a=mild, zone 3 perisinusoidal, 1b=moderate, zone 3, perisinusoidal, 1c=portal/periportal only, 2=zone 3 and periportal, any combination, 3=bridging, 4=cirrhosis. Fibrosis stages 1a, 1b, 1c recoded as 1, so the possible range of values for fibrosis stage was 0-4. Change in fibrosis stage has a possible range of -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement). (NCT01529268)
Timeframe: 52 weeks

Interventionunits on a scale (Mean)
DR Cysteamine Bitartrate Capsule-0.3
DR Cysteamine Bitartrate Placebo-0.1

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Change in Weight (kg)

(NCT01529268)
Timeframe: 52 weeks

Interventionkg (Mean)
DR Cysteamine Bitartrate Capsule6.3
DR Cysteamine Bitartrate Placebo7.8

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Change in Fasting Serum Glucose

(NCT01529268)
Timeframe: 52 weeks

Interventionmg/dL (Mean)
DR Cysteamine Bitartrate Capsule1
DR Cysteamine Bitartrate Placebo5

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Change in Fasting Insulin

(NCT01529268)
Timeframe: 52 weeks

InterventionμU/mL (Mean)
DR Cysteamine Bitartrate Capsule6
DR Cysteamine Bitartrate Placebo10

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Change in Diastolic Blood Pressure

(NCT01529268)
Timeframe: 52 weeks

InterventionmmHg (Mean)
DR Cysteamine Bitartrate Capsule-1
DR Cysteamine Bitartrate Placebo1

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Change in Body-mass Index Z-score

(NCT01529268)
Timeframe: 52 weeks

InterventionSD (Mean)
DR Cysteamine Bitartrate Capsule-0.1
DR Cysteamine Bitartrate Placebo0

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Change in Body-mass Index

(NCT01529268)
Timeframe: 52 weeks

Interventionkg/m^2 (Mean)
DR Cysteamine Bitartrate Capsule0.8
DR Cysteamine Bitartrate Placebo1.1

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Improvement in Nonalcoholic Fatty Liver Disease (NAFLD)

Centrally scored and masked assessment of histologic improvement in Nonalcholic Fatty Liver Disease (NAFLD) between the baseline liver biopsy and follow-up biopsy after 52 weeks of treatment, where improvement is defined as: (1) decrease in the NAFLD Activity Score (NAS) of 2 or more and (2) no worsening of fibrosis. (NCT01529268)
Timeframe: 52 weeks

Interventionparticipants (Number)
DR Cysteamine Bitartrate Capsule25
DR Cysteamine Bitartrate Placebo18

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Change in Waist Circumference

(NCT01529268)
Timeframe: 52 weeks

Interventioncm (Mean)
DR Cysteamine Bitartrate Capsule2.5
DR Cysteamine Bitartrate Placebo2.3

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Change in Systolic Blood Pressure

(NCT01529268)
Timeframe: 52 weeks

InterventionmmHg (Mean)
DR Cysteamine Bitartrate Capsule3
DR Cysteamine Bitartrate Placebo2

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Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)

Change from baseline in the NAFLD Activity Score (NAS), which is a composite score equal to the sum of the steatosis grade (0-3), lobular inflammation grade (0-3), and hepatocellular ballooning grade (0-2), from centralized pathologist scoring of liver biopsies. The overall scale of the NAS is 0-8, with higher scores indicating more severe disease. The outcome measure, change from baseline in NAFLD Activity Score (NAS), has a possible range from -8 to +8, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome. Components of the NAS are scored as follows: Steatosis grade 0=<5% steatosis, 1=5-33% steatosis, 2=34-66% steatosis, 3=>66% steatosis. Lobular inflammation grade=amount of lobular inflammation (combines mononuclear, fat granulomas, and polymorphonuclear (pmn) foci): 0=0, 1=<2 under 20x magnification, 2=2-4 under 20x magnification, 3=>4 under 20x magnification. Hepatocellular ballooning 0=none, 1=mild, 2=more than mild. (NCT01529268)
Timeframe: 52 weeks

Interventionunits on a scale (Mean)
DR Cysteamine Bitartrate Capsule-0.8
DR Cysteamine Bitartrate Placebo-0.8

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Reduction in MRI-determined Hepatic Fat Fraction

Change from baseline in MRI Proton Density Fat Fraction (PDFF) (%). (NCT01529268)
Timeframe: 52 weeks

Interventionpercentage of PDFF (Mean)
DR Cysteamine Bitartrate Capsule-5.3
DR Cysteamine Bitartrate Placebo-2.6

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Resolution of NASH

Patients with a change from a histological diagnosis of definite NASH or indeterminate for NASH to not NASH at end of treatment (NCT01529268)
Timeframe: 52 weeks

Interventionparticipants (Number)
DR Cysteamine Bitartrate Capsule4
DR Cysteamine Bitartrate Placebo2

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Steatosis: Change in Score

Change from baseline in steatosis score. Steatosis score is based on central pathologist grading of liver biopsies: 0=<5% steatosis; 1=5-33% steatosis, 2=34-66% steatosis, 3=>66% steatosis. Change in steatosis score has a possible range of -3 to +3, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement). (NCT01529268)
Timeframe: 52 weeks

Interventionunits on a scale (Mean)
DR Cysteamine Bitartrate Capsule-0.3
DR Cysteamine Bitartrate Placebo-0.4

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Steatosis: Patients With Improvement

Improvement in steatosis defined as any decrease in steatosis grade comparing 52-week biopsy to baseline. (NCT01529268)
Timeframe: 52 weeks

Interventionparticipants (Number)
DR Cysteamine Bitartrate Capsule26
DR Cysteamine Bitartrate Placebo33

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Change in Pediatric Quality of Life Inventory (PedsQL) Score

Pediatric Quality of Life Inventory (PedsQL) version 4.0 is completed by both the child and parent/caregiver, and is composed of 23 items comprising 4 dimensions: Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. Scores are transformed on a scale from 0 to 100, with higher scores indicating better health-related quality of life. Physical Health Summary Score =Physical Functioning Scale Score. Psychosocial Health Summary Score = Sum of items over the number of items answered in the Emotional, Social, and School Functioning Scales. (NCT01529268)
Timeframe: 52 weeks

,
Interventionunits on a scale (Mean)
Self-reported physical healthSelf-reported psychosocial healthParent/guardian-reported physical healthParent/guardian-reported psychosocial health
DR Cysteamine Bitartrate Capsule4445
DR Cysteamine Bitartrate Placebo5556

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Change in Serum Aminotransferase and Gamma-glutamyl Transpeptidase

(NCT01529268)
Timeframe: 52 weeks

,
InterventionU/L (Mean)
Alanine aminotransferaseAspartate aminotransferaseGamma-glutamyl transpeptidase
DR Cysteamine Bitartrate Capsule-53-31-10
DR Cysteamine Bitartrate Placebo-8-4-1

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Average Difference Between Morning and Non-Morning Log White Blood Cell (WBC) Cystine Values

The primary analysis of WBC cystine was performed using the natural log transformed WBC cystine level; the log transformation is a normalizing transformation. For each participant, the difference between the morning and corresponding non-morning log WBC cystine value (non-morning minus morning) at each monthly visit during the Cystagon® phase (Months 1, 2, and 3) was computed and these differences were averaged. The average difference between morning and non-morning log WBC cystine value was similarly computed for each participant during the RP103 phase (Months 5, 6, and 7). The primary analysis compared within-subject pairs (Cystagon® phase paired with RP103 phase) of non-morning minus morning average differences of log WBC cystine level. (NCT01733316)
Timeframe: While taking Cystagon® (Months 1, 2, 3): within 15 minutes pre-morning (AM) and pre-non AM dose. During 3 months of RP103 (Months 5, 6, 7): 30 minutes post-AM and post-evening (PM) dose.

Interventionlog [nmol ½ cystine/mg protein] (Mean)
Cystagon® Phase-0.229
RP103 Phase0.080

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Area Under the Plasma Concentration Time Curve From Time Point 0 Through the Last Measurable Point (AUC0-t) for Plasma Cysteamine

"Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered." (NCT01733316)
Timeframe: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose

Interventionhr*mg/L (Mean)
Cystagon® dosing periodRP103 dosing period
Halitosis Substudy Participants7.89.4

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Halitosis Substudy: Expired Air DMS Concentrations

"Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered." (NCT01733316)
Timeframe: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose 30 min post-dose, 2, 3, 4 and 6 hours post-dose. While taking RP103 (Month 4, 5, or 7): Within 15 min. prior to morning dose. 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose

Interventionnmol/L (Mean)
Cystagon®, within 15 minutes prior to doseCystagon®, 30 minutes post doseCystagon®, 1 hour post morning doseCystagon®, 2 hours post morning doseCystagon®, 3 hours post morning doseCystagon®, 4 hours post morning doseCystagon®, 6 hours post morning doseRP103, within 15 minutes prior to doseRP103, 1 hour post morning doseRP103, 2 hours post morning doseRP103, 3 hours post morning doseRP103, 4 hours post morning doseRP103, 5 hours post morning doseRP103, 6 hours post morning doseRP103, 8 hours post morning doseRP103, 10 hours post morning doseRP103, 12 hours post morning dose
Halitosis Substudy Participants4.74.76.911.911.28.84.44.65.45.17.78.611.28.55.75.24.3

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Halitosis Substudy: Maximum Plasma Concentration (Cmax) for Plasma Cysteamine

"Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of dimethylsulfide (DMS) in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state pharmacokinetic (PK) samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered." (NCT01733316)
Timeframe: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose

Interventionmg/L (Mean)
Cystagon® dosing periodRP103 dosing period
Halitosis Substudy Participants3.52.9

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Halitosis Substudy: Time to Cmax (Tmax) for Plasma Cysteamine

"Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered." (NCT01733316)
Timeframe: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose

Interventionhour (Mean)
Cystagon® dosing periodRP103 dosing period
Halitosis Substudy Participants1.23.2

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Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs

AE: any untoward medical occurrence that does not necessarily have a causal relationship with study drug. SAE: any untoward medical occurrence that at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; or is medically significant, and though not included in the above list, is an important medical event, according to the Investigator. Treatment-emergent adverse events (TEAEs) occurred after first dose of study drug. Clinically significant abnormalities in laboratory values (hematology, blood chemistry, urinalysis), electrocardiograms (ECGs), vital signs, and physical examinations were to be reported as adverse events and so are included in this summary of TEAEs (NCT01733316)
Timeframe: From first dose of study drug to 7 days after last dose. Median duration of exposure was 91 days (range 82-108) for Cystagon® phase, 119 days (range 98-137) for the RP103 phase, and 861 days (range 30 - 1350) during the long-term RP-103 phase.

,,
InterventionParticipants (Count of Participants)
At least 1 TEAEAt least 1 TEAE-related to study drugAt least 1 grade ≥ 3 TEAEAt least 1 serious TEAEAt least 1 TEAE leading to discontinuation
Cystagon® Phase314550
Long-Term Phase321813131
RP103 Phase3820460

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Mean White Blood Cell (WBC) Cystine Concentration at Each Visit

Blood samples were taken 30 minutes after the morning RP103 dose at each study visit to determine White Blood Cell (WBC) cystine concentration. WBC cystine concentrations were determined using liquid chromatography. (NCT01744782)
Timeframe: Day 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Month 6, Month 9, Month 12, Month 15, Month 18, Study Exit

Interventionnmol 1/2 Cystine/mg protein (Mean)
Day 1Week 2Week 4Week 6Week 8Week 10Week 12Month 6Month 9Month 12Month 15Month 18Study Exit
RP1033.17092.28991.84742.34030.95891.12191.18282.72502.01960.80121.24430.73560.8197

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Area Under the Plasma Concentration Versus Time Curve (AUC) of Cysteamine

Blood samples were collected and plasma cysteamine concentration was determined using liquid chromatography. AUC values were estimated using non-compartmental analysis methods. AUClast was defined as the area under the plasma concentration versus time curve, from time 0 to the time of the last measurable concentration (720 minutes). AUCinf was defined as the area under the plasma concentration-versus-time curve from time 0 to infinity. (NCT01744782)
Timeframe: 30 minutes after the morning RP103 dose at Month 6 (prior to Protocol Amendment 1) or 0 (pre-dose), 30 minutes, 2, 3, 4, 6, 8, 10, and 12 hours after the morning RP103 dose at Month 6 for those enrolled under Protocol Amendment 1 or later

Interventionmin*mg/L (Mean)
AUClastAUCinf
RP103206231

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Time of the Maximum Observed Plasma Concentration (Tmax) of Cysteamine

Blood samples were collected and plasma cysteamine concentration was determined using liquid chromatography. The time of the maximum observed plasma concentration (Tmax) of cysteamine was determined directly from the data. (NCT01744782)
Timeframe: 30 minutes after the morning RP103 dose at Month 6 (prior to Protocol Amendment 1) or 0 (pre-dose), 30 minutes, 2, 3, 4, 6, 8, 10, and 12 hours after the morning RP103 dose at Month 6 for those enrolled under Protocol Amendment 1 or later

Interventionminutes (Mean)
RP103199

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Number of Participants With Adverse Events

Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs). An AE/adverse experience was any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. For additional information regarding adverse events, please see the safety section of the record. (NCT01744782)
Timeframe: Day 1 through study exit

InterventionParticipants (Count of Participants)
RP10317

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Maximum Observed Plasma Concentration (Cmax) of Cysteamine

Blood samples were collected and plasma cysteamine concentration was determined using liquid chromatography. The maximum observed plasma concentration (Cmax) of cysteamine was determined directly from the data. (NCT01744782)
Timeframe: 30 minutes after the morning RP103 dose at Month 6 (prior to Protocol Amendment 1) or 0 (pre-dose), 30 minutes, 2, 3, 4, 6, 8, 10, and 12 hours after the morning RP103 dose at Month 6 for those enrolled under Protocol Amendment 1 or later

Interventionmg/L (Mean)
RP1031.26

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Change From Baseline in Friedreich Ataxia Rating Scale

"The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit.~Ataxia was assessed using the Friedreich Ataxia Rating Scale (FARS). FARS comprises a functional ataxia staging score of overall mobility (score 0 to 6), an assessment of the activities of daily living (ADL) (score 0 to 36) and a neurological assessment (score from 0 to 117) which is composed of bulbar (score 0-11), upper limb (score 0- 36) and lower limb (score 0-16), peripheral nerve (score 0-26) and upright stability/gait (score 0-28). The scores were summed to calculate the total score which ranges from 0 to 159. A higher score indicates a greater level of disability." (NCT02023866)
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24

Interventionunits on a scale (Mean)
Week 4Week 8Week 12Week 16Week 20Week 24
Cysteamine Bitartrate Delayed-release16.913.915.919.416.520.5

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Change From Baseline in Glutathione

(NCT02023866)
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24

Interventionµmol/L (Mean)
Week 4Week 8Week 12Week 16Week 20Week 24
Cysteamine Bitartrate Delayed-release16.8141.510.288.751.4122.4

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Change From Baseline in Glutathione Disulfide

(NCT02023866)
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24

Interventionµmol/L (Mean)
Week 4Week 8Week 12Week 16Week 20Week 24
Cysteamine Bitartrate Delayed-release29.4-9.818.8-11.20.8-11.5

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Change From Baseline in Gross Motor Function

"The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit.~Retarded motor development was assessed using the Gross Motor Function Measure (GMFM)-88 which consists of 88 items scored on a scale of 0 to 3:~0: Does not initiate the task;~Initiates the task (completes < 10%);~Partially completes the task (10 to 99%);~Completes the task (100%).~The 88 items are grouped into five dimensions: 1) lying and rolling, 2) sitting, 3) crawling and kneeling, 4) standing, and 5) walking, running and jumping. Scores are expressed as a percentage of the maximum score for that dimension. The total score is the average of the 5 the percentage scores where higher scores indicate better performance." (NCT02023866)
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24

Interventionunits on a scale (Mean)
Week 4Week 8Week 12Week 16Week 20Week 24
Cysteamine Bitartrate Delayed-release0.40.90.54.44.02.2

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Change From Baseline in Jamar Dynamometer Hand Strength

"The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit.~Myopathy was assessed using standard grip strength evaluation, which measures hand strength in both hands using a Jamar dynamometer." (NCT02023866)
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24

Interventionkg (Mean)
Week 4 - Left handWeek 8 - Left handWeek 12 - Left handWeek 16 - Left handWeek 20 - Left handWeek 24 - Left handWeek 4 - Right handWeek 8 - Right handWeek 12 - Right handWeek 16 - Right handWeek 20 - Right handWeek 24 - Right hand
Cysteamine Bitartrate Delayed-release1.31.11.30.00.71.30.51.61.60.70.91.2

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Change From Baseline in Lactic Acid

(NCT02023866)
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24

Interventionmmol/L (Mean)
Week 4Week 8Week 12Week 16Week 20Week 24
Cysteamine Bitartrate Delayed-release0.20.40.30.10.10.0

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Change From Baseline in Modified Lansky Play Performance Scale

"The investigator selected the 2 most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms were assessed at each subsequent study visit.~Reduced activities of daily living was assessed using the modified Lansky Play Performance Scale, completed by parents based on their child's activity in the past week, where 100=fully active; 90=minor restrictions in strenuous physical activity; 80=active, gets tired more quickly; 70=greater restriction of play, less time spent in play activity; 60=up and around, active play minimal; quieter activities; 50=lying around much of the day; no active playing, all quiet play and activities; 40=mainly in bed; quiet activities; 30=bedbound; needs assistance even for quiet play; 20=sleeps often; play limited to very passive activities; 10=doesn't play or get out of bed; 5=unresponsive 0=dead" (NCT02023866)
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24

Interventionunits on a scale (Mean)
Week 4Week 8Week 12Week 16Week 20Week 24
Cysteamine Bitartrate Delayed-release-2.0-6.0-2.02.0-4.0-6.0

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Change From Baseline in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Sections I-IV

"The NPMDS evaluates the progression of mitochondrial disease in pediatric patients in 4 domains:~I - Current Function (vision, hearing, communication, feeding, and mobility) with scores ranging from 0 to 21; II -System Specific Involvement (seizures, encephalopathy, bleeding diathesis or coagulation defects, gastrointestinal, endocrine, respiratory, cardiovascular, renal, liver, and blood) with scores ranging from 0 to 30.~III - Current Clinical Assessment (growth and development over past 6 months, vision, strabismus and eye movement, myopathy, ataxia, pyramidal, extrapyramidal, and neuropathy) with scores ranging from 0 to 28; and IV - Quality of Life with scores ranging from 0 to 25. For sections I-III, higher scores reflect more severe disease. For Section IV, a higher score reflects a lower quality of life." (NCT02023866)
Timeframe: Baseline through Week 24

Interventionunits on a scale (Mean)
Section ISection IISection IIISection IV
Cysteamine Bitartrate Delayed-release-0.30.1-0.60.0

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Change From Baseline in 6 Minute Walk Test

"The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: Myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit.~Myopathy was assessed using the 6 minute walk test, which measures the distance walked in a 6 minute walk test." (NCT02023866)
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24

Interventionmeters (Mean)
Week 4Week 8Week 12Week 16Week 20Week 24
Cysteamine Bitartrate Delayed-release-23.5-36.2-14.5-21.321.3-18.9

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Change From Baseline in Barry-Albright Dystonia Scale Total Score

"The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit.~Dystonia symptoms were assessed using the Barry-Albright Dystonia Scale for Dystonia. Participants were assessed for dystonia in each of the following regions: eyes, mouth, neck, trunk, and each upper and lower extremity (8 body regions) on a scale from 0 (absent) to 4 (severe symptoms). The individual scores were summed to calculate the total score which ranges from 0 (dystonia absent) to 32 (severe dystonia)." (NCT02023866)
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24

Interventionunits on a scale (Mean)
Week 4Week 8Week 12Week 16Week 20Week 24
Cysteamine Bitartrate Delayed-release1.30.70.30.3-0.70.7

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Change From Baseline in Sputum Bacterial Load

Change from baseline through to Day 21 in log10 cfu/ml transformed total gram negative sputum bacterial load (NCT03000348)
Timeframe: Baseline through Day 21/End of Study

,,,,,
Interventionlog 10 cfu/ml (Mean)
Day 7 change from baselineDay 14 change from baselineDay 21 change from baseline
150mg, Three Times Per Day-1.28-1.24-0.26
300mg, Three Times Per Day-1.03-0.98-0.87
450mg, Once Per Day-1.030.12-1.22
450mg, Twice Per Day-1.7-1.32-1.04
High Dose, Three Times Per Day-0.250.330.93
Placebo-2.1-1.38-0.18

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Safety and Tolerability Assessed by the Number of Subjects With Adverse Events

Assessed by variables such as adverse events (AEs), laboratory assessments, physical examinations, and vital signs. (NCT03000348)
Timeframe: Baseline through Day 21/End of Study

,,,,,
Interventionparticipants (Number)
Number of AEsNumber of SAEs1 or more AEsSeverity of AE mildSeverity of AE moderateSeverity of AE severeAEs leading to drug discontinuationNauseaVomitingInsomniaRashArthralgiaDecreased appetiteHaemoptysisOropharyngeal painAbdominal painBreath odour
150mg, Three Times Per Day4021156015221111110
300mg, Three Times Per Day4501045115213022120
450mg, Once Per Day2911064013200100100
450mg, Three Times Per Day3611376013120110102
450mg, Twice Per Day3311265113201101001
Placebo301972010000002010

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Change From Baseline in Weight

Weight (kg) by visit - ANCOVA with observed data (NCT03000348)
Timeframe: Baseline through Day 21/End of Study

,,,,,
Interventionkg (Mean)
Day 7Day 14Day 21
150mg, Three Times Per Day0.790.961.30
300mg, Three Times Per Day0.250.55-0.28
450mg, Once Per Day0.831.711.50
450mg, Three Times Per Day0.360.890.34
450mg, Twice Per Day0.671.040.52
Placebo0.960.851.37

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Change From Baseline in Sputum IL8

Sputum IL-8 Levels by Visit - Covariate Adjusted ANCOVA with Observed Data ITT Population (NCT03000348)
Timeframe: Baseline through Day 21/End of Study

,,,,,
Interventionpg/mL (Mean)
Day 7 change from baselineDay 14 Change from baselineDay 21 change from baseline
150mg, Three Times Per Day-5511-33653-19778
300mg, Three Times Per Day-2663-6136631
450mg, Once Per Day-17864-26528-16043
450mg, Three Times Per Day-25785221-10671
450mg, Twice Per Day11157431672831
Placebo-26088-288569576

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Change From Baseline in Neutrophil Elastase Levels

Actual values and change from baseline in neutrophil elastase levels were summarized using descriptive statistics by visit for each treatment group and each TDD group for the ITT Population. (NCT03000348)
Timeframe: Baseline through Day 21/End of Study

,,,,,
Interventionng/mL (Mean)
Day 7 change from baselineDay 14 change from baselineDay 21 change from baseline
150mg, Three Times Per Day704-7208171
300mg, Three Times Per Day-15769-14083-14591
450mg, Once Per Day23431-3804853
450mg, Three Times Per Day513514660-2558
450mg, Twice Per Day-19623-12014-21002
Placebo-4659-3706-1000

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Change From Baseline in Jarad and Sequeiros Symptom Score Questionnaire

The Jarad and Sequeiros Symptom Questionnaire (Jarad, 2012) is a simple participant-completed questionnaire that assesses and evaluates change in participant symptoms related to different aspects of respiratory function during a CF exacerbation. The questionnaire consists of 4 questions, each answered on a 4-point scale ranging from 1 (best) to 4 (worst). A range of minimum 4 to maximum16.Jarad and Sequeiros Questionnaire Score - changes from baseline at day 7 and day 14 (NCT03000348)
Timeframe: changes from baseline at day 7 and day 14

,,,,,
Interventionunits on a scale (Mean)
change from baseline to day 7change from baseline to day 14
150mg, Three Times Per Day-1.4-2.0
300mg, Three Times Per Day-2.4-3.1
450mg, Once Per Day-1.9-2.9
450mg, Three Times Per Day-3.1-4.2
450mg, Twice Per Day-3.3-4.3
Placebo-2.6-3.2

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Change From Baseline in FEV1

Change from Baseline in FEV1 Percent Predicted (%) - Covariate Adjusted ANCOVA with Observed Data ITT Population (NCT03000348)
Timeframe: Baseline through Day 21/End of Study

,,,,,
Interventionpercentage of predicted (Mean)
Day 7 change from baselineDay 14 change from baselineDay 21 change from baseline
150mg, Three Times Per Day6.98.96.5
300mg, Three Times Per Day4.95.36.4
450mg, Once Per Day4.44.04.7
450mg, Three Times Per Day3.77.56.3
450mg, Twice Per Day11.813.68.9
Placebo7.99.29.5

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Change From Baseline in CFRSD-CRISS

Mean Change from Baseline in Cystic Fibrosis Respiratory Symptom Diary (CFRSD)-Chronic Respiratory Infection Symptom Scale (CRISS) CRFSD-CRISS:The CFRSD is a 16-item PROM to evaluate the effect of treatment on the severity of symptoms of acute respiratory infections associated with CF (i.e., CFRSD-CRISS) and to assess the emotional and activity impacts of these symptoms. The overall CRISS score range is 0-100 with 100 being the most severe symptoms.The CFRSD-CRISS is a validated unidimensional scale based on a subset of 8 items from the CFRSD questionnaire that quantifies symptom severity for the previous 24 hours to capture the magnitude of symptoms in stable CF, during medically treated CF exacerbations, and during recover from an exacerbation. The 8 items on the CFRSD-CRISS were scored using a 5-point Likert scale ranging from 0 (no symptom) to 4 (the highest magnitude of severity). So score range of 0-32. (NCT03000348)
Timeframe: Baseline through to Day 21

,,,,,
Interventionunits on a scale (Mean)
Day 7 change from baselineDay 14 change from baselineDay 21 change from baseline
150mg, Three Times Per Day-11.9-15.5-15.8
300mg, Three Times Per Day-10.5-14.8-12.9
450mg, Once Per Day-18.1-24.3-23.2
450mg, Three Times Per Day-17.8-23.922.0
450mg, Twice Per Day-19.1-28.1-19.9
Placebo-16.4-16.3-18.3

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Change From Baseline in CFQ-R

The CFQ-R is a disease-specific HRQOL (Health related quality of life) measure containing both generic and CF-specific scales and measures functioning during the previous 2 weeks. Each CFQ-R scale yielded standardized scores ranging from 0 to 100; higher scores indicated better HRQOL (NCT03000348)
Timeframe: Baseline through Day 21/End of Study

,,,,,
Interventionunits on a scale (Mean)
Day 7 Change from baselineDay 14 change from baselineDay 21 change from baseline
150mg, Three Times Per Day12.019.725.2
300mg, Three Times Per Day15.921.824.8
450mg, Once Per Day12.224.430.6
450mg, Three Times Per Day19.628.637.3
450mg, Twice Per Day12.131.331.3
Placebo14.722.924.3

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Assessment of Blood Cysteamine Levels

Study Drug Plasma at Day 14 Safety Population (NCT03000348)
Timeframe: Day 14

Interventionng/ml (Mean)
Placebo10.0
450mg, Once Per Day515.11
150mg, Three Times Per Day102.45
450mg, Twice Per Day347.76
300mg, Three Times Per Day256.85
450mg, Three Times Per Day256.84

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Change From Baseline in C-Reactive Protein

Change from baseline in C-Reactive Protein at visits 7, 14 and 21 (NCT03000348)
Timeframe: Baseline through Day 21

,,,,,
Interventionnmol/L (Mean)
Day 7 change from baselineDay 14 change from baselineDay 21 change from baseline
150mg, Three Times Per Day-229.821-216.105-116.442
300mg, Three Times Per Day-120.193-111.272-23.421
450mg, Once Per Day-285.006-312.435-237.062
450mg, Three Times Per Day-281.752-294.13-225.787
450mg, Twice Per Day-318.933-215.242-198.759
Placebo-182.828-75.671-44.341

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Change From Baseline in BMI

BMI (kg/m^2) by Visit - ANCOVA with Observed Data ITT Population (NCT03000348)
Timeframe: Baseline through Day 21/End of Study

,,,,,
Interventionkg/m^2 for BMI (Mean)
BMI Day 7 change from baselineBMI Day 14 change from baselineBMI Day 21 change from baseline
150mg, Three Times Per Day0.280.340.47
300mg, Three Times Per Day0.150.23-0.02
450mg, Once Per Day0.320.640.55
450mg, Three Times Per Day0.150.320.12
450mg, Twice Per Day0.240.370.18
Placebo0.390.340.54

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Change From Baseline in Blood Leukocyte Count

Blood Leukocyte Count (10^9 leucocytes/L) by Visit - ANCOVA with Observed Data ITT Population (NCT03000348)
Timeframe: Baseline through Day 21/End of Study

,,,,,
Intervention10^9 leucocytes/L (Mean)
Day 7 change from baselineDay 14 change from baselineDay 21 change from baseline
150mg, Three Times Per Day-2.808-2.648-1.880
300mg, Three Times Per Day-2.575-0.193-0.127
450mg, Once Per Day-1.836-2.220-1.757
450mg, Three Times Per Day-2.863-4.066-3.316
450mg, Twice Per Day-2.482-3.419-1.763
Placebo-2.553-1.568-1.870

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Assessment of Sputum Cysteamine Levels

Study Drug Sputum Concentrations at Day 14 Safety Population (NCT03000348)
Timeframe: Day 14

Interventionng/ml (Mean)
Placebo150.0
450mg, Once Per Day682.8
150mg, Three Times Per Day150.0
450mg, Twice Per Day316.4
300mg, Three Times Per Day739.7
450mg, Three Times Per Day811.1

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