Page last updated: 2024-11-04

asparagine

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Description

Asparagine: A non-essential amino acid that is involved in the metabolic control of cell functions in nerve and brain tissue. It is biosynthesized from ASPARTIC ACID and AMMONIA by asparagine synthetase. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed) [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

asparagine : An alpha-amino acid in which one of the hydrogens attached to the alpha-carbon of glycine is substituted by a 2-amino-2-oxoethyl group. [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 CID6267
CHEMBL ID58832
CHEBI ID17196
SCHEMBL ID3126352
MeSH IDM0001818

Synonyms (121)

Synonym
asparagine, l-
(s)-2-amino-3-carbamoylpropanoic acid
l-aspartic acid beta-amide
aspartamic acid
CHEBI:17196 ,
(2s)-2-amino-3-carbamoylpropanoic acid
(2s)-2,4-diamino-4-oxobutanoic acid
l-asparagin
l-2-aminosuccinamic acid
nsc-82391
asparagine, l- (8ci)
l-b-asparagine
l-asparagine (9ci)
asparamide
crystal vi
l-aspartamine
2,4-diamino-4-oxobutanoic acid, (s)-
agedoite
l-2,4-diamino-4-oxobutanoic acid
altheine
l-asparatamine
(s)-asparagine
(s)-2,4-diamino-4-oxobutanoic acid
l-asparagine ,
(-)-asparagine
butanoic acid, 2,4-diamino-4-oxo-, (s)-
asparagine
l-beta-asparagine
2-aminosuccinamic acid, l-
alpha-aminosuccinamic acid
2-aminosuccinamic acid
l-asn
aspartic acid beta-amide
ASN ,
asparagine acid
70-47-3
C00152
l-asparagine, bioreagent, suitable for cell culture, suitable for insect cell culture
l-asparagine, >=98% (hplc)
asn nh3+ cooh
DB00174
asparagine (van)
AC-4657
3C28F6A9-E581-4255-ACCF-F75597AB288F
h-asn-oh
A0542
asparagine anhydrous
7ng0a2tuhq
CHEMBL58832
l-asparagine anhydrous
BMSE000030
l-beta-asparagine (van)
nor benzphetamine hydrochloride
A-9031
AKOS006239067
BMSE000912
asparagine (l) hydrate
pharmakon1600-01301002
nsc-760099
nsc760099
a-aminosuccinamic acid
aspartic acid b-amide
hsdb 7425
nsc 82391
5z33r5tko7 ,
unii-5z33r5tko7
einecs 200-735-9
S5571
gtpl4533
aspargine
asn-oh
AM81554
NCGC00344576-01
SCHEMBL3126352
.alpha.-aminosuccinamic acid
aspartic acid .beta. amide
mfcd00064401
us9138393, l-asparigine
bdbm181137
us9144538, l-asparigine
l-(+)-asparagine anhydrous
F1905-7151
asparagine anhydrous, united states pharmacopeia (usp) reference standard
l-asparagine, certified reference material, tracecert(r)
BP-23453
l-asparagine, vetec(tm) reagent grade, 98%
n-lauryl-n-methyltaurine
alpha amminosuccinamate
alpha-aminosuccinamate
l-2,4-diamino-4-oxobutanoate
2-aminosuccinamate
b2,4-(s)-diamino-4-oxo-utanoate
(s)-2,4-diamino-4-oxobutanoate
alpha amminosuccinamic acid
aspartamate
a-aminosuccinamate
aspartic acid beta amide
b2,4-(s)-diamino-4-oxo-utanoic acid
HY-N0667
CS-0009702
h-asn-oh h
4-imino-l-homoserine
DTXSID10883220 ,
Q29519883
STR07164
CCG-266117
p-aminosalicylicacidmagnesiumsalt
A937078
M02998
l-asparagine (h-asn-oh)
asparagine [hsdb]
asparagine [mi]
asparagine anhydrous [usp-rs]
asparagine [inci]
l-asparagine [fcc]
asparagine [who-dd]
EN300-67209
(-)-asparagine;asn;asparamide
asparagine anhydrous (usp-rs)
dtxcid901022769
Z1066276474

Research Excerpts

Toxicity

Study aimed to investigate correlation of L-asparaginase activity, anti-L-asp antibody, asparagine and glutamine levels with the risks of adverse events (AEs), especially anaphylaxis, in pediatric acute lymphoblastic leukemia patients.

ExcerptReferenceRelevance
" Several cytostatic drugs administered in the treatment of acute leukaemia in childhood are known to cause long-term adverse effects."( Minimising the long-term adverse effects of childhood leukaemia therapy.
Langebrake, C; Reinhardt, D; Ritter, J, 2002
)
0.31
" Specifically covered are the following aspects: nonfood and food sources; exposure from the environment and the diet; mechanism of formation in food from asparagine and glucose; asparagine-asparaginase relationships; Maillard browning-acrylamide relationships; quenching of protein fluorescence; biological alkylation of amino acids, peptides, proteins, and DNA by acrylamide and its epoxide metabolite glycidamide; risk assessment; neurotoxicity, reproductive toxicity, and carcinogenicity; protection against adverse effects; and possible approaches to reducing levels in food."( Chemistry, biochemistry, and safety of acrylamide. A review.
Friedman, M, 2003
)
0.32
" Mini-alphaA-crystallin also suppresses the toxic action of Abeta on rat pheochromocytoma (PC 12) cells."( Inhibition of amyloid fibrillogenesis and toxicity by a peptide chaperone.
Santhoshkumar, P; Sharma, KK, 2004
)
0.32
" The present 90-day toxicity study in F344/DuCrlCrj rats was conducted for safety assessment and to determine a no observed adverse effect level (NOAEL) of L-asparagine."( A 90-day toxicity study of L-asparagine, a food additive, in F344 rats.
Hashimoto, N; Hosokawa, K; Imaida, K; Kuno, T; Matsuda, Y; Saoo, K; Suzuki, S; Yamakawa, K; Yokohira, M, 2008
)
0.35
"Potentially toxic acrylamide is largely derived from heat-induced reactions between the amino group of the free amino acid asparagine and carbonyl groups of glucose and fructose in cereals, potatoes, and other plant-derived foods."( Review of methods for the reduction of dietary content and toxicity of acrylamide.
Friedman, M; Levin, CE, 2008
)
0.35
" Conversely, known activators of autophagy, such as lithium and rapamycin, displayed neuroprotection against this toxic compound."( Role of autophagy inhibitors and inducers in modulating the toxicity of trimethyltin in neuronal cell cultures.
Biagioni, F; Fabrizi, C; Fornai, F; Fumagalli, L; Lenzi, P; Pompili, E; Somma, F, 2012
)
0.38
" It appears to be safe in adults <40 years old, but has a unique spectrum of toxicities, the risks of which appear to increase with age."( Tolerability and toxicity of pegaspargase in adults 40 years and older with acute lymphoblastic leukemia.
Daley, RJ; Geyer, MB; Kabel, CC; Lavery, JA; Pappacena, JJ; Park, JH; Rajeeve, S; Stump, SE; Tallman, MS, 2021
)
0.62
"This study aimed to investigate the correlation of L-asparaginase (L-asp) activity, anti-L-asp antibody, asparagine and glutamine levels with the risks of adverse events (AEs), especially anaphylaxis, in pediatric acute lymphoblastic leukemia (ALL) patients who underwent polyethylene glycol-conjugated L-asp (PEG-asp)-contained treatment."( Correlation of L-asp Activity, Anti-L-asp Antibody, Asn and Gln With Adverse Events Especially Anaphylaxis Risks in PEG-asp-Contained Regime Treated Pediatric ALL Patients.
Chen, C; Chen, J; Huang, S; Shen, S; Wu, J; Zhang, S,
)
0.13

Pharmacokinetics

differences in pharmacokinetic properties between asparaginases make it difficult to predict the degree of asparagine depletion. Liposomes coated with the poly(amino acid) poly(hydroxyethyl-l-asparagine) (PHEA) were evaluated at low lipid doses and upon repeated administration.

ExcerptReferenceRelevance
" Because of its rapid half-life (T1/2) of approximately five minutes, intravenous (IV) infusion of large doses (approximately 100 mg) are required in patients treated for myocardial infarction."( Pharmacokinetic and distribution analysis of variant forms of tissue-type plasminogen activator with prolonged clearance in rat.
Blue, Y; Henson, K; Horgan, P; Larsen, GR; Metzger, M, 1989
)
0.28
" Subsequent elimination from plasma was monoexponential with a half-life of 6 +/- 1 days."( Pharmacokinetics of PEG-L-asparaginase and plasma and cerebrospinal fluid L-asparagine concentrations in the rhesus monkey.
Balis, FM; Berg, SL; Godwin, KS; McCully, CL; Poplack, DG, 1993
)
0.29
" We conclude that different L-asparaginase preparations are not readily interchangeable and that changes in the preparation, dosage or schedule require careful observation and possibly pharmacokinetic monitoring."( Pharmacokinetics and drug monitoring of L-asparaginase treatment.
Boos, J, 1997
)
0.3
" Purification and radioiodination of each of the five recombinant AT proteins permitted pharmacokinetic analysis of their individual clearance in rabbits."( Mutation of any site of N-linked glycosylation accelerates the in vivo clearance of recombinant rabbit antithrombin.
Ananthanarayanan, VS; Blajchman, MA; Ni, H; Sheffield, WP; Smith, IJ, 2000
)
0.31
"Asparaginase comes from different biological sources and the various preparations have different pharmacokinetic properties, and their tendency to induce side-effects is different."( Comparison of intramuscular therapy with Erwinia asparaginase and asparaginase Medac: pharmacokinetics, pharmacodynamics, formation of antibodies and influence on the coagulation system.
Albertsen, BK; Avramis, VI; Carlsen, NT; Ingerslev, J; Jakobsen, P; Müller, HJ; Schmiegelow, K; Schrøder, H, 2001
)
0.31
" In this study, the pharmacokinetic behavior of liposomes coated with the poly(amino acid) poly(hydroxyethyl-l-asparagine) (PHEA) was evaluated at low lipid doses and upon repeated administration in rats."( Pharmacokinetics of poly(hydroxyethyl-l-asparagine)-coated liposomes is superior over that of PEG-coated liposomes at low lipid dose and upon repeated administration.
Carstens, MG; Hennink, WE; Oussoren, C; Romberg, B; Snel, CJ; Storm, G, 2007
)
0.34
" At relapse, there were significant pharmacokinetic and pharmacodynamic differences attributable to ASP preparation and antibody status."( Comparison of native E. coli and PEG asparaginase pharmacokinetics and pharmacodynamics in pediatric acute lymphoblastic leukemia.
Cheng, C; Gajjar, A; Hak, LJ; Hijiya, N; Liu, W; Panetta, JC; Pui, CH; Relling, MV, 2009
)
0.35
" However, pronounced interpatient variability, differences in pharmacokinetic properties between asparaginases and the formation of asparaginase antibodies make it difficult to predict the degree of asparagine depletion that will result from a given dose of asparaginase."( Asparaginase pharmacokinetics and implications of therapeutic drug monitoring.
Asselin, B; Rizzari, C, 2015
)
0.42

Compound-Compound Interactions

ExcerptReferenceRelevance
"The German Multicentre acute lymphoblastic leukaemia (ALL) study group (GMALL) performed a pilot study using pegylated asparaginase (PEG-ASP) in combination with high-dose methotrexate as consolidation therapy in the 05/93 protocol."( Pegylated asparaginase in combination with high-dose methotrexate for consolidation in adult acute lymphoblastic leukaemia in first remission: a pilot study.
Arnold, R; Boos, J; Gökbuget, N; Hähling, D; Hartmann, F; Hoelzer, D; Ittel, TH; Langer, W; Mück, R; Müller, HJ; Peter, N; Rosen, O; Rothmann, F; Schwartz, S, 2003
)
0.32
" Cultivar 'Pingan 8' showed lower Zn concentrations in the grain than did cultivar 'Yangao 006' after nitrogen (N) combined with Zn application."( Effects of nitrogen combined with zinc application on glutamate, glutamine, aspartate and asparagine accumulation in two winter wheat cultivars.
Gao, W; Liu, H; Nie, Z; Rengel, Z; Wang, J; Zhao, P, 2018
)
0.48

Bioavailability

Asparagine could be a novel therapeutic strategy for KRAS-mutant cancers. Since MYC is a critical oncogene, our results uncover a molecular connection between MYC mRNA translation and asparagine bioavailability.

ExcerptReferenceRelevance
") administrations to obtain the disposition characteristics and bioavailability of this new anti-AIDS drug."( Pharmacokinetic study of a tripeptide HIV-1 protease inhibitor, KNI-174, in rats after intravenous and intraduodenal administrations.
Kiriyama, A; Kiso, Y; Mimoto, T; Takada, K, 1993
)
0.29
" Encapsulation significantly extended the intracellular retention time of the content in hepatocytes, which increased the bioavailability of the caspase inhibitor."( Design of a temporally and spatially controlled drug delivery system for the treatment of liver diseases in mice.
Akaike, T; Shibuya, I; Watanabe, Y, 2000
)
0.31
" Further optimization resulted in compound 11, a potent, selective, and orally bioavailable inhibitor of aggrecanase."( Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase inhibitors.
Arner, EC; Chao, M; Christ, D; Covington, MB; Decicco, CP; Liu, RQ; Magolda, RL; Newton, R; Pratta, MA; Qian, M; Reddy, G; Ribadeneira, MD; Shi, E; Tortorella, M; Wasserman, ZR; Wexler, RR; Yao, W, 2001
)
0.31
"To overcome the low bioavailability of our substituted acrylamide P1 benzamidine factor Xa inhibitors reported previously, neutral and less basic groups were used to replace the benzamidine."( Substituted acrylamides as factor Xa inhibitors: improving bioavailability by P1 modification.
Bhakta, C; Clizbe, L; Huang, B; Li, W; Park, G; Reed, A; Scarborough, RM; Sinha, U; Song, Y; Teng, W; Wong, P; Zhu, BY, 2002
)
0.31
" Sex hormone-binding globulin (SHBG) regulates the bioavailability of sex hormones to target tissues."( Asp327Asn polymorphism of sex hormone-binding globulin gene is associated with systemic lupus erythematosus incidence.
Cieślak, D; Gasik, R; Hrycaj, P; Jagodziński, PP; Lianeri, M; Piotrowski, P; Wudarski, M; Łacki, JK, 2010
)
0.36
" In conclusion, site-specific CBG N-glycosylation regulates the bioavailability of cortisol in inflamed environments by fine-tuning the RCL proteolysis by endogenous and exogenous elastases."( Asn347 Glycosylation of Corticosteroid-binding Globulin Fine-tunes the Host Immune Response by Modulating Proteolysis by Pseudomonas aeruginosa and Neutrophil Elastase.
Grant, OC; Packer, NH; Sumer-Bayraktar, Z; Thaysen-Andersen, M; Venkatakrishnan, V; Woods, RJ, 2016
)
0.43
" Here we show that asparagine bioavailability strongly influences metastatic potential."( Asparagine bioavailability governs metastasis in a model of breast cancer.
Carey, LA; D'Santos, CS; Dickopf, S; Erard, N; Fish, L; Gable, AL; Goodarzi, H; Hannon, GJ; Harrell, JC; Khan, S; Kim, SY; Knott, SRV; Maceli, AR; Papachristou, EK; Perou, CM; Poulogiannis, G; Soto, M; Turgeon, MO; Wagenblast, E; Wagner, M; Wilkinson, JE, 2018
)
0.48
" These results indicate that dual blockade of macropinocytosis and asparagine bioavailability could be a novel therapeutic strategy for KRAS-mutant cancers."( Dual blockade of macropinocytosis and asparagine bioavailability shows synergistic anti-tumor effects on KRAS-mutant colorectal cancer.
Hanada, K; Hirata, W; Honma, S; Itatani, Y; Kawada, K; Kiyasu, Y; Maekawa, H; Masui, H; Miyoshi, H; Mizuno, R; Nishikawa, G; Nishikawa, Y; Obama, K; Ogawa, R; Okamoto, M; Sakai, Y; Sasazuki, T; Shirasawa, S; Taketo, MM; Toda, K, 2021
)
0.62
" Since MYC is a critical oncogene, our results uncover a molecular connection between MYC mRNA translation and asparagine bioavailability and shed light on a potential to target MYC oncogene post-transcriptionally through asparagine restriction."( Asparagine bioavailability regulates the translation of MYC oncogene.
Batra, S; Chen, C; Davé, U; Fan, J; Jiang, J; Kapur, R; Liu, Y; Misra, J; Seim, G; Srivastava, S; Staschke, KA; Wek, RC; Zhang, C; Zhang, J; Zhong, M; Zhou, J; Zhou, L, 2022
)
0.72

Dosage Studied

PEG-L-asparaginase is generally well tolerated in patients with advanced solid tumors. Dose-response curves have shown more than 70% inhibition of tumor growth with a glutamine concentration of 50% and asparagine concentration of 25%.

ExcerptRelevanceReference
" The single-channel conductance was not altered by any of the three inhibitors, and the slopes of log-log dose-response curves at low concentrations and desensitization did not appear to be affected."( Inhibitors of asparagine-linked oligosaccharide processing alter the kinetics of the nicotinic acetylcholine receptor.
Covarrubias, M; Kopta, C; Steinbach, JH, 1989
)
0.28
" The dose-response relationship showed that the relative potency of the compounds is C-1 less than C-2 less than JSTX."( Newly synthesized analogues of the spider toxin block the crustacean glutamate receptor.
Aramaki, Y; Endo, Y; Hashimoto, Y; Kawai, N; Nakajima, T; Shudo, K, 1987
)
0.27
" Dose-response curves have shown more than 70% inhibition of tumor growth with a glutamine concentration of 50% and an asparagine concentration of 25%."( Amino acid requirements of a rat sarcoma as determined by a stem cell assay.
Chance, WT; Franco, RS; Martelo, OJ; Miller, TJ; Popp, MB,
)
0.13
" Two other non-T-/non-B-cells showed unique ara-C dose-response curves."( Differences in chemotherapeutic susceptibility of human T-, B-, and non-T-/non-B-lymphocytes in culture.
Arkin, H; Holland, JF; Ohnuma, T, 1980
)
0.26
" We conclude that different L-asparaginase preparations are not readily interchangeable and that changes in the preparation, dosage or schedule require careful observation and possibly pharmacokinetic monitoring."( Pharmacokinetics and drug monitoring of L-asparaginase treatment.
Boos, J, 1997
)
0.3
", at the standard dosage of 10,000 IU/m2, q 3 days x 8 (first exposure)."( L-asparagine depletion and L-asparaginase activity in children with acute lymphoblastic leukemia receiving i.m. or i.v. Erwinia C. or E. coli L-asparaginase as first exposure.
Aricò, M; Bruno, A; Conter, V; D'Incalci, M; Diomede, L; Gavazzi, L; Lo Nigro, L; Milani, M; Paganini, M; Rizzari, C; Sparano, P; Zucchetti, M, 2000
)
0.31
"We conclude that PEG-L-asparaginase is generally well tolerated in patients with advanced solid tumors, and a dosage of 2,000 IU/m2 by intramuscular injection every 2 weeks results in significant depletion of serum L-asparagine."( A phase I and pharmacodynamic evaluation of polyethylene glycol-conjugated L-asparaginase in patients with advanced solid tumors.
Dorr, RT; Fanta, P; Hersh, EM; Salmon, SE; Taylor, CW, 2001
)
0.31
" Some of the point mutations caused shifts in the GABA dose-response curve, indicating that the mutations changed the apparent affinity of the receptor for GABA."( Volatile anesthetic actions on the GABAA receptors: contrasting effects of alpha 1(S270) and beta 2(N265) point mutations.
Harrison, NL; Jenkins, A; Nishikawa, K; Paraskevakis, I, 2002
)
0.31
" In this study a second polymorphism (Ile-568 to Asn) has been found in heterozygous dosage in three of 85 normal subjects and in three of 45 patients with chronic lymphocytic leukemia."( An Ile-568 to Asn polymorphism prevents normal trafficking and function of the human P2X7 receptor.
Barden, JA; Dao-Ung, LP; Fuller, SJ; Gu, BJ; Li, C; Petrou, S; Shemon, AN; Sluyter, R; Smart, ML; Wiley, JS, 2003
)
0.32
" Uremic toxins were also incubated with purified human albumin, and dose-response experiments with the two most toxic agents in terms of protein damage (guanidine and guanidinopropionic acid) were carried out."( Plasma protein aspartyl damage is increased in hemodialysis patients: studies on causes and consequences.
D'Aniello, A; De Santo, NG; Galletti, P; Ingrosso, D; Lombardi, C; Perna, AF; Satta, E, 2004
)
0.32
" Although the mechanisms behind these observations are still not clear yet, the use of PHEA-liposomes appears beneficial when single low lipid doses and/or repeated dosing schedules are being applied."( Pharmacokinetics of poly(hydroxyethyl-l-asparagine)-coated liposomes is superior over that of PEG-coated liposomes at low lipid dose and upon repeated administration.
Carstens, MG; Hennink, WE; Oussoren, C; Romberg, B; Snel, CJ; Storm, G, 2007
)
0.34
" Dosage analysis of PTEN was carried out using multiplex ligation-dependent probe amplification (MLPA)."( Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.
Anckarsäter, H; Betancur, C; Buxbaum, JD; Cai, G; Chaste, P; Gillberg, C; Goldsmith, J; Hollander, E; Leboyer, M; Nygren, G; Rastam, M; Reichert, J; Silverman, JM; Smith, CJ; Verloes, A, 2007
)
0.34
" In comparison with pyridoxal, pyridoxine, and ascorbic acid, PM exerted the highest inhibition activity against AA formation, and a clear dose-response was observed."( Effect of pyridoxamine on acrylamide formation in a glucose/asparagine model system.
Arribas-Lorenzo, G; Morales, FJ, 2009
)
0.35
" Mutations of L427R, N428R and L431K in transmembrane domain-I-segment 6 (IS6) of the channel significantly attenuated the Rg(3) action and caused rightward shifts in dose-response curves."( Mutations Leu427, Asn428, and Leu431 residues within transmembrane domain-I-segment 6 attenuate ginsenoside-mediated L-type Ca(2+) channel current inhibitions.
Bae, CS; Choi, SH; Hwang, SH; Kim, BR; Kim, HC; Lee, BH; Lee, JH; Lee, SM; Nah, SY; Oh, JW; Pyo, MK; Rhim, H; Shin, TJ, 2009
)
0.35
" The amino sulfoximine 5 exhibits different dose-response behavior when incubated with an ASNase-sensitive MOLT-4 cell line (MOLT-4S), supporting the hypothesis that sulfoximine 5 exerts its effect by inhibiting hASNS in the cell."( A sulfoximine-based inhibitor of human asparagine synthetase kills L-asparaginase-resistant leukemia cells.
Ahn, YM; Hegazy, L; Hiratake, J; Ikeuchi, H; Otokawa, T; Richards, NG; Watanabe, B, 2012
)
0.38
" Patients in the homozygous SS group demonstrated higher basal FSH levels, required more dosage of exogenous gonadotropin for ovarian stimulation, and had fewer numbers of oocytes retrieved compared with patients in the homozygous NN and heterozygous groups."( The Ser680Asn polymorphism in the follicle-stimulating hormone receptor gene is associated with the ovarian response in controlled ovarian hyperstimulation.
Du, J; Hong, L; Huang, X; Li, L; Shi, H; Sun, X; Zhang, H; Zhang, Z; Zhou, W, 2015
)
0.42
" The proposed approach, chito-pegylation, is effective for regulating the catalytic and pharmacokinetic properties of asparaginase, and is promising for the development of prolonged action dosage forms for other enzyme therapeutics."( [PEG-chitosan branched copolymers to improve the biocatalytic properties of Erwinia carotovora recombinant L-asparaginase].
Kudryashova, EV; Sokolov, NN; Suhoverkov, KV,
)
0.13
" The intent of this review is manifold: a) to summarize the physiological role of CYP enzymes and hepatic-biliary transporters; b) to discuss the mechanism(s) involved in the purported liver injury caused by bosentan; c) to tabulate the numerous clinical drug-drug interaction studies involving the physiological interplay with CYP and/or transporters; d) to provide some perspectives on dosing strategy of bosentan."( Glycosylation of α2δ1 subunit: a sweet talk with Cav1.2 channels.
Lazniewska, J; Weiss, N, 2016
)
0.43
" In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice."( Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice.
Koyanagi, S; Kusunose, N; Matsunaga, N; Ohdo, S; Shiromizu, S, 2018
)
0.48
" However, limited intra-individual variability is a precondition for targeted dosing and the diagnosis of SI."( Therapeutic Drug Monitoring of Asparaginase: Intra-individual Variability and Predictivity in Children With Acute Lymphoblastic Leukemia Treated With PEG-Asparaginase in the AIEOP-BFM Acute Lymphoblastic Leukemia 2009 Study.
Attarbaschi, A; Boos, J; Gerss, J; Lanvers-Kaminsky, C; Möricke, A; Nath, C; Rizzari, C; Schrappe, M; Smisek, P; Stary, J; Würthwein, G; Zimmermann, M; Zucchetti, M, 2020
)
0.56
" Seed bioassay and whole-plant dose-response experiments were conducted using commercial IMI herbicides."( Ser-653-Asn substitution in the acetohydroxyacid synthase gene confers resistance in weedy rice to imidazolinone herbicides in Malaysia.
Ahmad-Hamdani, MS; Mazlan, N; Ruzmi, R, 2020
)
0.56
" However, recommended doses and dosing intervals are mainly empirically determined."( Evaluation of PEG-L-asparaginase in asparagine suppression and anti-drug antibody development in healthy Beagle dogs: A multi-phase preclinical study.
Feenstra, LR; Gehring, R; König, T; Krupa, A; Lammens, T; Prinsen, HCMT; Teske, E; van Geijswijk, IM; Vandemeulebroecke, K, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (7)

RoleDescription
nutraceuticalA product in capsule, tablet or liquid form that provide essential nutrients, such as a vitamin, an essential mineral, a protein, an herb, or similar nutritional substance.
micronutrientAny nutrient required in small quantities by organisms throughout their life in order to orchestrate a range of physiological functions.
human metaboliteAny mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
Saccharomyces cerevisiae metaboliteAny fungal metabolite produced during a metabolic reaction in Baker's yeast (Saccharomyces cerevisiae).
Escherichia coli metaboliteAny bacterial metabolite produced during a metabolic reaction in Escherichia coli.
mouse metaboliteAny mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
plant metaboliteAny eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
[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 (5)

ClassDescription
amino acid zwitterionThe zwitterionic form of an amino acid having a negatively charged carboxyl group and a positively charged amino group.
asparagineAn alpha-amino acid in which one of the hydrogens attached to the alpha-carbon of glycine is substituted by a 2-amino-2-oxoethyl group.
L-alpha-amino acidAny alpha-amino acid having L-configuration at the alpha-carbon.
aspartate family amino acidAn L-alpha-amino acid which is L-aspartic acid or any of the essential amino acids biosynthesised from it (asparagine, lysine, methionine, threonine and isoleucine). A closed class.
proteinogenic amino acidAny of the 23 alpha-amino acids that are precursors to proteins, and are incorporated into proteins during translation. The group includes the 20 amino acids encoded by the nuclear genes of eukaryotes together with selenocysteine, pyrrolysine, and N-formylmethionine. Apart from glycine, which is non-chiral, all have L configuration.
[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 (20)

PathwayProteinsCompounds
Aspartate Metabolism1430
Ammonia Recycling1227
Canavan Disease1430
Hypoacetylaspartia1430
Inner Membrane Transport7862
tRNA Charging5227
tRNA Charging 22225
Asparagine Biosynthesis612
Asparagine Metabolism412
Alanine,Aspartic acid and Asparagine metabolism ( Alanine,Aspartic acid and Asparagine metabolism )2237
Protein Synthesis: Asparagine804
Nsp9 interactions (COVID-19 Disease Map)8330
mRNA, protein, and metabolite inducation pathway by cyclosporin A213
tRNA charging pathway023
superpathway of aspartate and asparagine biosynthesis; interconversion of aspartate and asparagine012
asparagine biosynthesis II07
AtMetExpress overview0109
Biochemical pathways: part I0466
Amino acid metabolism094
Metabolic reprogramming in colon cancer029

Protein Targets (6)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Carbonic anhydrase 1Homo sapiens (human)KA11.30000.02001.72197.4000AID1397319
Carbonic anhydrase 2Homo sapiens (human)KA100.00000.01101.42737.8000AID1397320
Carbonic anhydrase-like protein, putativeTrypanosoma cruzi strain CL BrenerKA100.00000.14002.80507.5400AID1397322
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (35)

Processvia Protein(s)Taxonomy
one-carbon metabolic processCarbonic anhydrase 1Homo sapiens (human)
morphogenesis of an epitheliumCarbonic anhydrase 2Homo sapiens (human)
positive regulation of synaptic transmission, GABAergicCarbonic anhydrase 2Homo sapiens (human)
positive regulation of cellular pH reductionCarbonic anhydrase 2Homo sapiens (human)
angiotensin-activated signaling pathwayCarbonic anhydrase 2Homo sapiens (human)
regulation of monoatomic anion transportCarbonic anhydrase 2Homo sapiens (human)
secretionCarbonic anhydrase 2Homo sapiens (human)
regulation of intracellular pHCarbonic anhydrase 2Homo sapiens (human)
neuron cellular homeostasisCarbonic anhydrase 2Homo sapiens (human)
positive regulation of dipeptide transmembrane transportCarbonic anhydrase 2Homo sapiens (human)
regulation of chloride transportCarbonic anhydrase 2Homo sapiens (human)
carbon dioxide transportCarbonic anhydrase 2Homo sapiens (human)
one-carbon metabolic processCarbonic anhydrase 2Homo sapiens (human)
L-cystine transportNeutral amino acid transporter AHomo sapiens (human)
amino acid transportNeutral amino acid transporter AHomo sapiens (human)
glutamine transportNeutral amino acid transporter AHomo sapiens (human)
L-alanine transportNeutral amino acid transporter AHomo sapiens (human)
L-cystine transportNeutral amino acid transporter AHomo sapiens (human)
proline transportNeutral amino acid transporter AHomo sapiens (human)
L-serine transportNeutral amino acid transporter AHomo sapiens (human)
threonine transportNeutral amino acid transporter AHomo sapiens (human)
hydroxyproline transportNeutral amino acid transporter AHomo sapiens (human)
synaptic transmission, glutamatergicNeutral amino acid transporter AHomo sapiens (human)
proline transmembrane transportNeutral amino acid transporter AHomo sapiens (human)
cognitionNeutral amino acid transporter AHomo sapiens (human)
L-aspartate import across plasma membraneNeutral amino acid transporter AHomo sapiens (human)
transport across blood-brain barrierNeutral amino acid transporter AHomo sapiens (human)
chloride transmembrane transportNeutral amino acid transporter AHomo sapiens (human)
L-serine import across plasma membraneNeutral amino acid transporter AHomo sapiens (human)
L-alanine import across plasma membraneNeutral amino acid transporter AHomo sapiens (human)
L-glutamate transmembrane transportNeutral amino acid transporter AHomo sapiens (human)
amino acid transportNeutral amino acid transporter B(0)Homo sapiens (human)
glutamine transportNeutral amino acid transporter B(0)Homo sapiens (human)
glutamine secretionNeutral amino acid transporter B(0)Homo sapiens (human)
neutral amino acid transportNeutral amino acid transporter B(0)Homo sapiens (human)
L-serine transportNeutral amino acid transporter B(0)Homo sapiens (human)
erythrocyte differentiationNeutral amino acid transporter B(0)Homo sapiens (human)
symbiont entry into host cellNeutral amino acid transporter B(0)Homo sapiens (human)
protein homotrimerizationNeutral amino acid transporter B(0)Homo sapiens (human)
L-aspartate import across plasma membraneNeutral amino acid transporter B(0)Homo sapiens (human)
transport across blood-brain barrierNeutral amino acid transporter B(0)Homo sapiens (human)
L-glutamine import across plasma membraneNeutral amino acid transporter B(0)Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (23)

Processvia Protein(s)Taxonomy
arylesterase activityCarbonic anhydrase 1Homo sapiens (human)
carbonate dehydratase activityCarbonic anhydrase 1Homo sapiens (human)
protein bindingCarbonic anhydrase 1Homo sapiens (human)
zinc ion bindingCarbonic anhydrase 1Homo sapiens (human)
hydro-lyase activityCarbonic anhydrase 1Homo sapiens (human)
cyanamide hydratase activityCarbonic anhydrase 1Homo sapiens (human)
arylesterase activityCarbonic anhydrase 2Homo sapiens (human)
carbonate dehydratase activityCarbonic anhydrase 2Homo sapiens (human)
protein bindingCarbonic anhydrase 2Homo sapiens (human)
zinc ion bindingCarbonic anhydrase 2Homo sapiens (human)
cyanamide hydratase activityCarbonic anhydrase 2Homo sapiens (human)
L-cystine transmembrane transporter activityNeutral amino acid transporter AHomo sapiens (human)
chloride channel activityNeutral amino acid transporter AHomo sapiens (human)
amino acid transmembrane transporter activityNeutral amino acid transporter AHomo sapiens (human)
L-alanine transmembrane transporter activityNeutral amino acid transporter AHomo sapiens (human)
L-aspartate transmembrane transporter activityNeutral amino acid transporter AHomo sapiens (human)
L-cystine transmembrane transporter activityNeutral amino acid transporter AHomo sapiens (human)
L-glutamine transmembrane transporter activityNeutral amino acid transporter AHomo sapiens (human)
L-proline transmembrane transporter activityNeutral amino acid transporter AHomo sapiens (human)
L-serine transmembrane transporter activityNeutral amino acid transporter AHomo sapiens (human)
L-threonine transmembrane transporter activityNeutral amino acid transporter AHomo sapiens (human)
symporter activityNeutral amino acid transporter AHomo sapiens (human)
L-hydroxyproline transmembrane transporter activityNeutral amino acid transporter AHomo sapiens (human)
virus receptor activityNeutral amino acid transporter B(0)Homo sapiens (human)
protein bindingNeutral amino acid transporter B(0)Homo sapiens (human)
amino acid transmembrane transporter activityNeutral amino acid transporter B(0)Homo sapiens (human)
L-aspartate transmembrane transporter activityNeutral amino acid transporter B(0)Homo sapiens (human)
L-glutamine transmembrane transporter activityNeutral amino acid transporter B(0)Homo sapiens (human)
L-serine transmembrane transporter activityNeutral amino acid transporter B(0)Homo sapiens (human)
symporter activityNeutral amino acid transporter B(0)Homo sapiens (human)
antiporter activityNeutral amino acid transporter B(0)Homo sapiens (human)
ligand-gated channel activityNeutral amino acid transporter B(0)Homo sapiens (human)
signaling receptor activityNeutral amino acid transporter B(0)Homo sapiens (human)
metal ion bindingNeutral amino acid transporter B(0)Homo sapiens (human)
neutral L-amino acid transmembrane transporter activityNeutral amino acid transporter B(0)Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (13)

Processvia Protein(s)Taxonomy
cytosolCarbonic anhydrase 1Homo sapiens (human)
extracellular exosomeCarbonic anhydrase 1Homo sapiens (human)
cytoplasmCarbonic anhydrase 2Homo sapiens (human)
cytosolCarbonic anhydrase 2Homo sapiens (human)
plasma membraneCarbonic anhydrase 2Homo sapiens (human)
myelin sheathCarbonic anhydrase 2Homo sapiens (human)
apical part of cellCarbonic anhydrase 2Homo sapiens (human)
extracellular exosomeCarbonic anhydrase 2Homo sapiens (human)
cytoplasmCarbonic anhydrase 2Homo sapiens (human)
plasma membraneCarbonic anhydrase 2Homo sapiens (human)
apical part of cellCarbonic anhydrase 2Homo sapiens (human)
plasma membraneNeutral amino acid transporter AHomo sapiens (human)
centrosomeNeutral amino acid transporter AHomo sapiens (human)
intermediate filamentNeutral amino acid transporter AHomo sapiens (human)
plasma membraneNeutral amino acid transporter AHomo sapiens (human)
cell surfaceNeutral amino acid transporter AHomo sapiens (human)
membraneNeutral amino acid transporter AHomo sapiens (human)
melanosomeNeutral amino acid transporter AHomo sapiens (human)
synapseNeutral amino acid transporter AHomo sapiens (human)
extracellular exosomeNeutral amino acid transporter AHomo sapiens (human)
plasma membraneNeutral amino acid transporter B(0)Homo sapiens (human)
basal plasma membraneNeutral amino acid transporter B(0)Homo sapiens (human)
membraneNeutral amino acid transporter B(0)Homo sapiens (human)
melanosomeNeutral amino acid transporter B(0)Homo sapiens (human)
extracellular exosomeNeutral amino acid transporter B(0)Homo sapiens (human)
plasma membraneNeutral amino acid transporter B(0)Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (9)

Assay IDTitleYearJournalArticle
AID681113TP_TRANSPORTER: inhibition of L-tryptophan uptake in Xenopus laevis oocytes2001The Journal of biological chemistry, May-18, Volume: 276, Issue:20
Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters.
AID80836Tested for its reversal effect on growth of H4 cells at 330 ug/mL concentrations of L-aspargine and DL-threo-beta-fluoroaspartate1982Journal of medicinal chemistry, May, Volume: 25, Issue:5
DL-threo-beta-Fluoroaspartate and DL-threo-beta-fluoroasparagine: selective cytotoxic agents for mammalian cells in culture.
AID26797Partition coefficient (logP)1987Journal of medicinal chemistry, Oct, Volume: 30, Issue:10
Quantitative structure-activity relationships of the bitter thresholds of amino acids, peptides, and their derivatives.
AID80832Tested for its reversal effect on growth of H4 cells at 133 ug/mL concentrations of L-aspargine and DL-threo-beta-fluoroaspartate1982Journal of medicinal chemistry, May, Volume: 25, Issue:5
DL-threo-beta-Fluoroaspartate and DL-threo-beta-fluoroasparagine: selective cytotoxic agents for mammalian cells in culture.
AID233320Bitter threshold value; NB denotes 'Not bitter'1987Journal of medicinal chemistry, Oct, Volume: 30, Issue:10
Quantitative structure-activity relationships of the bitter thresholds of amino acids, peptides, and their derivatives.
AID1397320Activation of human CA2 by stopped-flow CO2 hydration assay
AID1397319Activation of human CA1 by stopped-flow CO2 hydration assay
AID1397321Activation of Leishmania donovani chagasi CA preincubated for 15 mins followed by CO2 addition by stopped-flow assay
AID1397322Activation of Trypanosoma cruzi CA preincubated for 15 mins followed by CO2 addition by stopped-flow assay
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (6,597)

TimeframeStudies, This Drug (%)All Drugs %
pre-19902019 (30.60)18.7374
1990's1362 (20.65)18.2507
2000's1697 (25.72)29.6817
2010's1180 (17.89)24.3611
2020's339 (5.14)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials41 (0.60%)5.53%
Reviews275 (4.03%)6.00%
Case Studies151 (2.21%)4.05%
Observational2 (0.03%)0.25%
Other6,350 (93.12%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]