Page last updated: 2024-12-04

chlorothiazide

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Description

Chlorothiazide is a thiazide diuretic that was first synthesized in 1957. It works by inhibiting the reabsorption of sodium and chloride ions in the distal convoluted tubule of the kidneys, leading to increased urine output. Chlorothiazide is used to treat high blood pressure and edema. It is also used to prevent the formation of kidney stones in people with high levels of calcium in their urine. Chlorothiazide is effective in treating high blood pressure, but it can have side effects, such as hypokalemia, hyponatremia, and hyperglycemia. Chlorothiazide is also a relatively common cause of drug-induced lupus. Chlorothiazide is studied to improve its effectiveness and reduce its side effects. Researchers are also investigating new uses for chlorothiazide, such as treating certain types of cancer. It is important to note that chlorothiazide can interact with other medications, so it is important to talk to a doctor before taking it.'

Chlorothiazide: A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812) [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

thiazide : Heterocyclic compound with sulfur and nitrogen in the ring. [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]

chlorothiazide : 4H-1,2,4-benzothiadiazine 1,1-dioxide in which the hydrogen at position is substituted by chlorine and that at position 7 is substituted by a sulfonamide group. A diuretic, it is used for treatment of oedema and hypertension. [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 CID2720
CHEMBL ID842
CHEMBL ID3392493
CHEBI ID3640
SCHEMBL ID22329
MeSH IDM0004186

Synonyms (215)

Synonym
chlorothiazidum
6-chloro-4h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
AC-18732
BIDD:GT0635
clorotiazida
AB00051940-04
BRD-K88682005-001-05-9
2h-1,2,4-benzothiadiazine-7-sulfonamide, 6-chloro-, 1,1-dioxide
DIVK1C_000675
KBIO1_000675
6-chloro-2h-1,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
saluretil
nsc25693
6-chloro-7-sulfamoyl-2h-1,4-benzothiadiazine 1,1-dioxide
chlorothiazid
clotride
chlorthiazide
saluric
chlorurit
salisan
neo-dema
diuril
thiazide
diurite
warduzide
diutrid
chlorosal
2h-1,4-benzothiadiazine-7-sulfonamide, 6-chloro-, 1,1-dioxide
minzil
diurilix
nsc-25693
flumen
diuresal
chlortiazid
alurene
yadalan
component of aldoclor
salunil
urinex
wln: t66 bswm enj hg iszw
chlotride
EU-0100254
6-chloro-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
6-chloro-7-sulfamoyl-2h-1,2,4-benzothiadiazine 1,1-dioxide
chlorothiazide, thiazide diuretic
6-chloro-1,1-dioxo-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide
SPECTRUM_000134
PRESTWICK_56
NCGC00015242-01
NCGC00015242-02
lopac-c-4911
cas-58-94-6
PRESTWICK3_000251
PRESTWICK2_000251
BSPBIO_000062
SPECTRUM5_001446
IDI1_000675
BPBIO1_000070
BSPBIO_002003
LOPAC0_000254
NCGC00091042-01
sk-chlorothiazide
hsdb 3030
chlorthiazidum
chlorothiazidum [inn-latin]
clorotiazida [inn-spanish]
ccris 5999
nsc 25693
einecs 200-404-9
diuril boluses, veterinary
clorotiazide [dcit]
chlorthiazid
58-94-6
C07461
chlorothiazide
DB00880
6-chloro-1,1-dioxo-1,2-dihydro-1lambda*6*-benzo[1,2,4]thiadiazine-7-sulfonic acid amide
chlorothiazide (jan/usp/inn)
D00519
NCGC00091042-04
NCGC00091042-03
MLS000028398 ,
smr000058429
KBIO3_001223
KBIOGR_000780
KBIO2_005730
KBIOSS_000594
KBIO2_003162
KBIO2_000594
SPBIO_000288
SPBIO_002281
SPECTRUM3_000342
PRESTWICK1_000251
PRESTWICK0_000251
SPECTRUM2_000154
SPECTRUM4_000280
NINDS_000675
SPECTRUM1500180
NCGC00091042-05
NCGC00015242-03
NCGC00091042-02
NCGC00015242-05
HMS2091C18
C 4911 ,
C2259
NCGC00015242-09
chebi:3640 ,
CHEMBL842
hydrochlorothiazide impurity, chlorothiazide-
HMS502B17
FT-0664953
HMS1568D04
HMS1920K15
NCGC00015242-04
HMS3259K15
HMS3260D10
HMS2095D04
NCGC00258525-01
tox21_200972
AKOS024319450
pharmakon1600-01500180
nsc-756682
nsc756682
tox21_110107
dtxcid802800
dtxsid0022800 ,
HMS2232N22
CCG-38953
NCGC00015242-07
NCGC00015242-06
NCGC00015242-10
NCGC00015242-08
chlrosal
diuril boluses
chloriazid
unii-77w477j15h
chlorothiazide [usp:inn:ban]
77w477j15h ,
clorotiazide
NCGC00015242-12
LP00254
S1641
AKOS015896601
6-chloro-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide
HMS3370A15
gtpl4835
chlorothiazide [vandf]
chlorothiazide [usp monograph]
chlorothiazide [inn]
chlorothiazide [hsdb]
chlorothiazide [mi]
chlorothiazide [orange book]
chlorothiazide [ep impurity]
chlorothiazide [jan]
chlorothiazide [green book]
chlorothiazide [who-dd]
chlorothiazide [usp impurity]
hydrochlorothiazide impurity a [ep impurity]
chlorothiazide [mart.]
hydrochlorothiazide impurity, chlorothiazide- [usp impurity]
HY-B0224
NC00500
SCHEMBL22329
tox21_110107_1
NCGC00015242-13
tox21_500254
NCGC00260939-01
bdbm39351
cid_2720
W-105353
diupres (salt/mix)
aldoclor (salt/mix)
6-chloro-4h-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide
AB00051940_06
AB00051940_05
mfcd00058576
CHEMBL3392493
chlorothiazide, european pharmacopoeia (ep) reference standard
6-chloro-2h-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide
chlorothiazide, united states pharmacopeia (usp) reference standard
HMS3655M13
chlorothiazide, pharmaceutical secondary standard; certified reference material
sr-01000075604
SR-01000075604-1
SR-01000075604-3
SR-01000075604-5
SBI-0050242.P004
HMS3712D04
SW219268-1
6-chloro-1,1-dioxo-4h-1lambda6,2,4-benzothiadiazine-7-sulfonamide
BCP24474
6-chloro-1,1-dioxo-4h-1$l^{6,2,4-benzothiadiazine-7-sulfonamide
6-chloro-1,1-dioxo-2h-1,2,4-benzothiadiazine-7-sulfonamide
Z1501480416
Q2603363
AS-11760
BRD-K88682005-001-07-5
SDCCGSBI-0050242.P005
NCGC00015242-19
6-chloro-4h-1,2,4-benzathiadiazine-7-sulfonamide-1,1-dioxide
D89501
chlorothiazide 100 microg/ml in acetonitrile
c03aa04
yadulan
chlorothiazide (mart.)
chlorothiazide (usp impurity)
chlorothiazide (ep impurity)
2h-1,2,4-benzothiadiazine-7-sulfonamide, 6-chloro-,1,1-dioxide
chlorothiazide (usp monograph)
exuril
6-chloro-1,1-dioxo-1,2-dihydro-1lambda*6*-benzo(1,2,4)thiadiazine-7-sulfonic acid amide
6-chloro-7-sulfamyl-1,2,4-benzothiadiazine 1,1-dioxide
ro-chlorozide
hydrochlorothiazide impurity, chlorothiazide-(usp impurity)
hydrochlorothiazide impurity a (ep impurity)

Research Excerpts

Overview

Chlorothiazide (CTZ) is a diuretic and is used to treat hypertension. It is a much more potent inhibitor of alkaline phosphatase than the other three diuretics.

ExcerptReferenceRelevance
"Chlorothiazide (CTZ) is a diuretic and is used to treat hypertension."( Effect of Antihypertensive Drug (Chlorothiazide) on Fibrillation of Lysozyme: A Combined Spectroscopy, Microscopy, and Computational Study.
Almutairi, GS; Alokail, MS; Altwaijry, N; Khan, MS; Shaik, GM, 2023
)
1.91
"Chlorothiazide (CTZ) is a poorly soluble diuretic agent. "( Preparation and characterisation of novel chlorothiazide potassium solid-state salt forms: Intermolecular self assembly suprastructures.
Corrigan, OI; Healy, AM; McCabe, T; O'Brien, JE; Paluch, KJ; Tajber, L, 2011
)
2.08
"Chlorothiazide is a much more potent inhibitor of alkaline phosphatase than the other three diuretics."( Inhibition of alkaline phosphatase by several diuretics.
Price, GH, 1980
)
0.98

Effects

Chlorothiazide has been shown to be almost ineffective as a diuretic agent per se. It has marked carbonic anhydrase inhibiting activity, increased CLi by about 25%.

ExcerptReferenceRelevance
"Chlorothiazide has been shown to be almost ineffective as a diuretic agent per se."( SULFONAMYL DIURETICS--MECHANISM OF ACTION AND THERAPEUTIC USE.
ROBERTS, KE, 1964
)
0.96
"2. Chlorothiazide, which has marked carbonic anhydrase inhibiting activity, increased CLi by about 25%."( Acute effects of thiazides, with and without carbonic anhydrase inhibiting activity, on lithium and free water clearance in man.
Boer, WH; Dorhout Mees, EJ; Koomans, HA, 1989
)
0.79

Treatment

Treatment with chlorothiazide, neutral phosphates or bicarbonate slightly reduced serum Ca below the levels in either positive or negative controls. Chlorothiazid treatment led to an alkalosis in brain.

ExcerptReferenceRelevance
"Chlorothiazide treatment led to an alkalosis in brain."( Effect of magnesium depletion and potassium depletion and chlorothiazide on intracellular pH in the rat, studied by 31P NMR.
Adam, WR; Craik, DJ; Kneen, M; Wellard, RM, 1989
)
1.24
"Treatment with chlorothiazide, neutral phosphates or bicarbonate slightly reduced serum Ca below the levels in either positive or negative controls."( Effects of selected therapeutic agents on urolithiasis induced by terephthalic acid in the male weanling Fischer 344 rat.
Chin, TY; Wolkowski-Tyl, R,
)
0.47
"Treatment with chlorothiazide lowered plasma potassium and raised plasma bicarbonate to normal levels (p = 0.05)."( Impaired renal acidification in infants with fetal alcohol syndrome.
Assadi, FK; Ziai, M, 1985
)
0.61

Toxicity

ExcerptReferenceRelevance
"Oral metolazone was noninferior to IV chlorothiazide for enhancing net UOP in patients with ADHF and loop diuretic resistance and was similarly safe with regard to renal function and electrolyte abnormalities."( Efficacy and Safety of Intravenous Chlorothiazide versus Oral Metolazone in Patients with Acute Decompensated Heart Failure and Loop Diuretic Resistance.
Devabhakthuni, S; Ivaturi, V; Jiang, A; Liu, T; Reed, BN; Shulenberger, CE, 2016
)
0.98

Pharmacokinetics

ExcerptReferenceRelevance
" The data were analyzed in terms of a two compartment pharmacokinetic model as previously reported (8)."( Effect of chlorothiazide on the pharmacokinetics of lithium in plasma and erythrocytes.
Hanin, I; Himmelhoch, JM; Mallinger, AG; Mallinger, J; Neil, JF; Poust, RI, 1976
)
0.66
" The elimination half-life in plasma was 10."( Single-dose and steady-state pharmacokinetics of doxazosin given in combination with chlorothiazide to hypertensive subjects.
Conway, EL; Drummer, OH; Howes, LG; Louis, WJ; McNeil, JJ; Meng, L; Raymond, K, 1989
)
0.5
"Individual pharmacokinetic parameters quantify the pharmacokinetics of an individual, while population pharmacokinetic parameters quantify population mean-kinetics, interindividual variability, and residual variability, including intraindividual variability and measurement error."( Evaluation of methods for estimating population pharmacokinetic parameters. II. Biexponential model and experimental pharmacokinetic data.
Beal, SL; Sheiner, LB, 1981
)
0.26
" Simulations incorporating specific SIWV values were compared to pharmacokinetic data from compounds exhibiting solubility induced non-proportional changes in absorption using absolute average fold-error."( Parameterization of small intestinal water volume using PBPK modeling.
Edginton, A; Fotaki, N; Maharaj, A, 2015
)
0.42

Bioavailability

The relative bioavailability of chlorothiazide from mucoadhesive polymeric compacts is compared to commercial oral suspension in pigs. A urinary excretion bioavailability study was conducted in 12 healthy male subjects.

ExcerptReferenceRelevance
"A urinary excretion bioavailability study was conducted in 12 healthy male subjects to evaluate three 250-mg and three 500-mg chlorothiazide tablet products."( Bioavailability of chlorothiazide tablets in humans.
Melikian, AP; Meyer, MC; Straughn, AB, 1979
)
0.79
" There was a good correlation between MATAAP and the extent of bioavailability of chlorothiazide, however, there was no correlation between TFASP and the extent of bioavailability of the drug."( Gastrointestinal absorption of chlorothiazide: evaluation of a method using salicylazosulfapyridine and acetaminophen as the marker compounds for determination of the gastrointestinal transit time in the dog.
Kawazoe, Y; Mizuta, H; Ogawa, K, 1990
)
0.79
" Fluoxetine is well absorbed after oral administration in both the fed and fasted states and demonstrates dose proportionality."( Fluoxetine: clinical pharmacology and physiologic disposition.
Aronoff, GR; Bergstrom, RF; Enas, GG; Farid, NA; Lemberger, L; Wolen, RL, 1985
)
0.27
" Plasma drug levels in rats showed a longer duration of action and greater bioavailability for the bioadhesive dosage form than for either albumin beads or drug powder alone."( Bioadhesive polymers as platforms for oral controlled drug delivery III: oral delivery of chlorothiazide using a bioadhesive polymer.
Ch'ng, HS; Longer, MA; Robinson, JR, 1985
)
0.49
" Excretion data indicated that the drug was poorly absorbed from the gastrointestinal tract."( The effect of dosage on the bioavailability of chlorothiazide administered in solution.
Corrigan, OI; O'Driscoll, KM, 1980
)
0.52
" When the dose did not exceed the solubility of the drug in the intestinal lumen, the fraction absorbed depended on the transit rate relative to the absorption rate and the pK alpha relative to the pH profile, but was independent of drug dose."( Physicochemical model for dose-dependent drug absorption.
Amidon, GL; Dressman, JB; Fleisher, D, 1984
)
0.27
"The bioavailability of chlorothiazide from oral tablets was examined under fasting and nonfasting conditions in healthy male volunteers."( Influence of food and fluid volume on chlorothiazide bioavailability: comparison of plasma and urinary excretion methods.
Barbhaiya, RH; Welling, PG, 1982
)
0.85
"The bioavailability of chlorothiazide was examined following single oral solution doses to eight healthy male volunteers."( Bioavailability of chlorothiazide from 50, 100, and 250 MG solution doses.
Craig, WA; Irwin, DS; Osman, MA; Patel, RB; Welling, PG,
)
0.77
"Based on the initial dissolution rate profiles in water, a slow-dissolving, an intermediate-dissolving, and a fast-dissolving chlorothiazide 250-mg tablet were selected for the bioavailability and bioequivalence study."( Thiazides IV: Comparison of dissolution with bioavailability of chlorothiazide tablets.
Cabana, BE; Knight, P; Prasad, VK; Shah, VP, 1982
)
0.71
"The bioavailability of an aqueous solution of chlorothiazide and three commercially available chlorothiazide tablets was assessed in adult mongrel dogs."( Chlorothiazide absorption from solution and tablet dosage forms in dogs.
Bates, TR; Ebling, WF; Murro, AF; Resetarits, DE; Voelker, FJ, 1981
)
1.96
" This particulate system may have potential use as a carrier for drugs that are poorly absorbed after oral administration."( Alginate-pectin-poly-L-lysine particulate as a potential controlled release formulation.
Krishnan, TR; Liu, P, 1999
)
0.3
"The quantitative structure-bioavailability relationship of 232 structurally diverse drugs was studied to evaluate the feasibility of constructing a predictive model for the human oral bioavailability of prospective new medicinal agents."( QSAR model for drug human oral bioavailability.
Topliss, JG; Yoshida, F, 2000
)
0.31
" The reported great similarity in apparent first-order absorption rate constants (k) of seven structurally diverse compounds between the two species were obtained."( Similarity in the linear and non-linear oral absorption of drugs between human and rat.
Chiou, WL; Chung, SM; Jeong, HY; Ma, C; Wu, TC, 2000
)
0.31
"The relative bioavailability of chlorothiazide from mucoadhesive polymeric compacts is compared to commercial oral suspension in pigs."( Relative bioavailability of chlorothiazide from mucoadhesive compacts in pigs.
Alfredson, T; Anne, P; Birudaraj, R; Jasti, BR; Li, X; Mahalingam, R; Neelam, K, 2009
)
0.93
"4, suggesting that ABCG2 plays a role in limiting chlorothiazide bioavailability in humans."( ABCG2 modulates chlorothiazide permeability--in vitro-characterization of its interactions.
Abonyi, T; Bánsághi, S; Beéry, E; Erdő, F; Herédi-Szabó, K; Jani, M; Kis, E; Krajcsi, P; Makai, I; Márki-Zay, J; Rajnai, Z; Sziráki, I; Tóth, GK, 2012
)
0.98
"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

Dissolution profiles were determined for nine methenamine, 14 nitrofurantoin, and six chlorothiazide dosage forms using a dissolution simulator. Data on demographic, clinical, fluid intake/output, and furosemide and chlorothsiazide dosing were collected. Observed relationships between chlorothazide dosage and absorption efficiency are consistent with previous suggestions that chlorothozide absorption from the GI tract is saturable.

ExcerptRelevanceReference
" Furosemide and ethacrynic acid, when used at the recommended dosage (1 mg/kg), would probably not produce a significant increase in free bilirubin in most infants."( Displacement of bilirubin from human albumin by three diuretics.
Ahlfors, CE; Rasmussen, F; Wennberg, RP, 1977
)
0.26
" Dosage levels were set at 5 mg."( Antihypertensive activity of a new agent, indapamide: a double-blind study.
Milliez, P; Tcherdakoff, P, 1975
)
0.25
" On the other hand, the dose-response relationship to carbachol, a cholinergic agonist resistant to cholinesterase degradation, was unaffected by CTZ."( The effect of chlorothiazide on neurally mediated contraction of rabbit bronchial smooth muscle.
Brunner, SL; Scott, JY; Tanaka, DT, 1992
)
0.64
" There was little difference between the total sodium and chloride output after each dose of clopamide, suggesting that 5 mg may have been close to the top of the dose-response curve."( Clopamide: plasma concentrations and diuretic effect in humans.
Christophidis, N; Conway, EL; Drummer, OH; Howes, LG; Louis, WJ; McNeil, JJ, 1987
)
0.27
"Bioadhesive polymers that bind to the gastric mucin or epithelial cell surface are useful in drug delivery for the purposes of (a) retaining a dosage from in the GI tract and (b) increasing the intimacy and duration of contact of drug with the absorbing membrane."( Bioadhesive polymers as platforms for oral controlled drug delivery III: oral delivery of chlorothiazide using a bioadhesive polymer.
Ch'ng, HS; Longer, MA; Robinson, JR, 1985
)
0.49
" Analysis of data at the four dosage levels for each subject is suggestive of the fact that chlorothiazide absorption is possibly an example of Michaelis-Menten kinetics."( Chlorothiazide absorption in humans--possible example of Michaelis-Menten kinetics.
Adebayo, GI; Mabadeje, AF, 1985
)
1.93
"Dissolution profiles were determined for nine methenamine, 14 nitrofurantoin, and six chlorothiazide dosage forms using a dissolution simulator."( In vivo-in vitro correlations with a commercial dissolution simulator. I: Methenamine, nitrofurantoin, and chlorothiazide.
Meyer, MC; Yau, MK, 1981
)
0.7
" Recoveries from commercial dosage forms ranged from 99."( Liquid chromatographic determination of methyldopa and methyldopa-thiazide combinations in dosage forms.
Ting, S, 1983
)
0.27
" This can be obtained by selection of the appropriate dosage regimen for a particular diuretic, such as once daily administration for "long-acting" and twice daily for "short-acting" thiazide-type diuretics."( Long-acting and short-acting diuretics in mild essential hypertension.
Chalmers, JP; Graham, JR; West, MJ; Wing, LM, 1982
)
0.26
" Observed relationships between chlorothiazide dosage and absorption efficiency are consistent with previous suggestions that chlorothiazide absorption from the GI tract is saturable and site specific."( Influence of food and fluid volume on chlorothiazide bioavailability: comparison of plasma and urinary excretion methods.
Barbhaiya, RH; Welling, PG, 1982
)
0.82
" These results add support to previous suggestions that the absorption of chlorothiazide from the gastrointestinal tract is saturable, and that the availability of chlorothiazide may be similar to that of hydrochlorothiazide when these compounds are administered in the same dosage range."( Bioavailability of chlorothiazide from 50, 100, and 250 MG solution doses.
Craig, WA; Irwin, DS; Osman, MA; Patel, RB; Welling, PG,
)
0.69
" The suitability of the method for pharmacokinetic studies was verified in a normal volunteer dosed with 250-mg (solution) and 500-mg (sustained-release tablet) acetazolamide formulations."( Quantitation of acetazolamide in plasma by high-performance liquid chromatography.
Brien, R; Hossie, RD; Mousseau, N; Sved, S, 1980
)
0.26
" Hypercalcemia and a history of nephrocalcinosis had prevented appropriate dosing of calcium prior to and during the first months of her hospital stay."( Pamidronate in a girl with chronic renal insufficiency dependent on parenteral nutrition.
Chesney, RW; Duke, JL; Frizzell, NK; Hak, EB; Jones, DP, 2003
)
0.32
" The variable dosage requirement of spironolactone in patients with cirrhosis and ascites is discussed in relation to these observations."( A comparison of the use of Aldactone and Aldactone A in the treatment of hepatic ascites.
GARSENSTEIN, M; RYDER, JA; SHALDON, S, 1963
)
0.24
" Moreover, the methods were successfully applied for the determination of HCZ and BZ and AM in pure form and pharmaceutical dosage forms."( Simultaneous determination of hydrochlorothiazide and benazepril hydrochloride or amiloride hydrochloride in presence of hydrochlorothiazide impurities: chlorothiazide and salamide by HPTLC method.
Abdelaleem, EA; Draz, ME; Naguib, IA; Zaazaa, HE, 2015
)
0.69
" The analysis results prove to be valid for analysis of the two active ingredients in raw materials and pharmaceutical dosage form through handling UV spectral data in range (220-350 nm)."( Linear support vector regression and partial least squares chemometric models for determination of Hydrochlorothiazide and Benazepril hydrochloride in presence of related impurities: a comparative study.
Abdelaleem, EA; Draz, ME; Naguib, IA; Zaazaa, HE, 2014
)
0.62
" Data on demographic, clinical, fluid intake/output, and furosemide and chlorothiazide dosing were collected."( Efficacy of sequential nephron blockade with intravenous chlorothiazide to promote diuresis in cardiac intensive care infants.
Akcan-Arikan, A; Bronicki, RA; Checchia, PA; Kennedy, C; Moffett, BS; Tsang, R, 2017
)
0.93
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
diureticAn agent that promotes the excretion of urine through its effects on kidney function.
antihypertensive agentAny drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism.
[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 (1)

ClassDescription
benzothiadiazineHeterocyclic compound of a ring with sulfur and two nitrogen atoms fused to a benzene ring. Members inhibit sodium-potassium-chloride symporters and are used as diuretics.
[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 (1)

PathwayProteinsCompounds
Chlorothiazide Action Pathway319

Protein Targets (39)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASEHomo sapiens (human)Potency1.12200.003245.467312,589.2998AID2517
Chain A, Beta-lactamaseEscherichia coli K-12Potency15.84890.044717.8581100.0000AID485294
acetylcholinesteraseHomo sapiens (human)Potency63.57060.002541.796015,848.9004AID1347395
USP1 protein, partialHomo sapiens (human)Potency354.81300.031637.5844354.8130AID743255
NFKB1 protein, partialHomo sapiens (human)Potency3.98110.02827.055915.8489AID895; AID928
GLS proteinHomo sapiens (human)Potency22.38720.35487.935539.8107AID624146
thyroid stimulating hormone receptorHomo sapiens (human)Potency16.53110.001318.074339.8107AID926; AID938
regulator of G-protein signaling 4Homo sapiens (human)Potency2.37780.531815.435837.6858AID504845
EWS/FLI fusion proteinHomo sapiens (human)Potency0.01480.001310.157742.8575AID1259255
nonstructural protein 1Influenza A virus (A/WSN/1933(H1N1))Potency0.31620.28189.721235.4813AID2326
retinoic acid nuclear receptor alpha variant 1Homo sapiens (human)Potency59.15430.003041.611522,387.1992AID1159552; AID1159553; AID1159555
estrogen-related nuclear receptor alphaHomo sapiens (human)Potency17.79660.001530.607315,848.9004AID1224821; AID1224849
arylsulfatase AHomo sapiens (human)Potency0.37931.069113.955137.9330AID720538
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency0.67020.035520.977089.1251AID504332
Bloom syndrome protein isoform 1Homo sapiens (human)Potency1,122.02000.540617.639296.1227AID2364; AID2528
transcriptional regulator ERG isoform 3Homo sapiens (human)Potency0.89130.794321.275750.1187AID624246
nuclear factor erythroid 2-related factor 2 isoform 1Homo sapiens (human)Potency19.96670.000627.21521,122.0200AID743202; AID743219
gemininHomo sapiens (human)Potency11.88560.004611.374133.4983AID624297
cytochrome P450 3A4 isoform 1Homo sapiens (human)Potency10.00000.031610.279239.8107AID884; AID885
muscarinic acetylcholine receptor M1Rattus norvegicus (Norway rat)Potency24.06820.00106.000935.4813AID943; AID944
lamin isoform A-delta10Homo sapiens (human)Potency0.89130.891312.067628.1838AID1487
Gamma-aminobutyric acid receptor subunit piRattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-1Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit deltaRattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-5Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-3Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-1Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-2Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-4Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-3Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-6Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-3Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
GABA theta subunitRattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit epsilonRattus norvegicus (Norway rat)Potency10.00001.000012.224831.6228AID885
ATP-dependent phosphofructokinaseTrypanosoma brucei brucei TREU927Potency37.93300.060110.745337.9330AID485368
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
ORF73Human gammaherpesvirus 8EC50 (µMol)75.00000.06008.134632.1400AID435023
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Ceullar Components (1)

Processvia Protein(s)Taxonomy
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)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (155)

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.
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.
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.
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.
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.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
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.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings 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.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
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.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347407qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical 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.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347425Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
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.
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.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347424RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
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).
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID1123564Diuretic activity in Wistar rat assessed as potassium level in excreted urine at 50 mg/kg, po measured after 0 to 5 hrs by flame photometric analysis relative to urea-treated control1979Journal of medicinal chemistry, Jan, Volume: 22, Issue:1
Synthesis and evaluation for diuretic activity of 1-substituted 6-chloro-5-sulfamylindolines.
AID190287Saluretic activity in rats after 0-5 hours, as potassium ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
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).
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]
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID190417Saluretic activity in rats after 5-24 hours, as sodium ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
AID232282Saluretic activity in rats after 0-24 hours, as ratio of Na+/K+ ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
AID190288Saluretic activity in rats after 0-5 hours, as sodium ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
AID29359Ionization constant (pKa)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
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).
AID172875Percent change in K+ in fasted rats at the dose of 30 mg/kg (po), 0-5 h1990Journal of medicinal chemistry, Jun, Volume: 33, Issue:6
Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives.
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).
AID977599Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM2013Molecular pharmacology, Jun, Volume: 83, Issue:6
Structure-based identification of OATP1B1/3 inhibitors.
AID29812Oral bioavailability in human2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
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).
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).
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]
AID453203Lipophilicity, log D of the compound2010Bioorganic & medicinal chemistry letters, Jan-01, Volume: 20, Issue:1
Development of an in silico model for human skin permeation based on a Franz cell skin permeability assay.
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).
AID1137229Diuretic activity in acute sodium loaded Wistar rat assessed as urine volume at 50 mg/kg, po measured for 0 to 5 hrs post drug dosing relative to urea1978Journal of medicinal chemistry, Apr, Volume: 21, Issue:4
Spiro[isobenzofuran-1(3H),4'-piperidines]. 3. Diuretic and antihypertensive properties of compounds containing a sulfur attached to nitrogen.
AID1761236Permeability of compound at pH 7.4 measured after 6 hrs by PAMPA assay2021European journal of medicinal chemistry, Feb-05, Volume: 2112-Propargylamino-naphthoquinone derivatives as multipotent agents for the treatment of Alzheimer's disease.
AID604743Displacement of radiolabeled warfarin from fatty acid containing human serum albumin site 1 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID1123562Diuretic activity in Wistar rat assessed as volume of excreted urine at 50 mg/kg, po measured after 0 to 5 hrs relative to urea-treated control1979Journal of medicinal chemistry, Jan, Volume: 22, Issue:1
Synthesis and evaluation for diuretic activity of 1-substituted 6-chloro-5-sulfamylindolines.
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]
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID190289Saluretic activity in rats after 5-24 hours, as chloride ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
AID172864Percent change in K+ in fasted rats at the dose of 10 mg/kg (iv), 0-5 h1990Journal of medicinal chemistry, Jun, Volume: 33, Issue:6
Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives.
AID1137239Diuretic activity in acute sodium loaded Wistar rat assessed as potassium level in urine at 50 mg/kg, po measured for 0 to 5 hrs post drug dosing by flame photometer relative to urea1978Journal of medicinal chemistry, Apr, Volume: 21, Issue:4
Spiro[isobenzofuran-1(3H),4'-piperidines]. 3. Diuretic and antihypertensive properties of compounds containing a sulfur attached to nitrogen.
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID1137244Diuretic activity in acute sodium loaded Wistar rat assessed as chloride level in urine at 50 mg/kg, po measured for 0 to 5 hrs post drug dosing by chloride analyzer relative to urea1978Journal of medicinal chemistry, Apr, Volume: 21, Issue:4
Spiro[isobenzofuran-1(3H),4'-piperidines]. 3. Diuretic and antihypertensive properties of compounds containing a sulfur attached to nitrogen.
AID232284Saluretic activity in rats after 5-24 hours, as ratio of Na+/K+ ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
AID409956Inhibition of mouse brain MAOB2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID453204Permeability in human skin after 48 hrs by Franz cell permeability assay2010Bioorganic & medicinal chemistry letters, Jan-01, Volume: 20, Issue:1
Development of an in silico model for human skin permeation based on a Franz cell skin permeability assay.
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.
AID604741Displacement of radiolabeled warfarin from fatty acid-free human serum albumin site 1 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID175818Diuretic activity in rats at time intervals of 0-5 hours1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID190285Saluretic activity in rats after 0-24 hours, as sodium ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
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).
AID1150383Diuretic activity in po dosed albino Wistar-TNO rat assessed as increase in urinary volume measured for 5 hrs1976Journal of medicinal chemistry, Jul, Volume: 19, Issue:7
A new class of diuretics with the 1,4-dioxino(2,3-g)quinolone structure.
AID190286Saluretic activity in rats after 0-5 hours, as chloride ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1889700Permeability of compound at pH 7.4 by PAMPA assay2022European journal of medicinal chemistry, Mar-15, Volume: 232Novel D
AID175817Diuretic activity in rats at time intervals of 0-24 hours1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
AID977602Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM2013Molecular pharmacology, Jun, Volume: 83, Issue:6
Structure-based identification of OATP1B1/3 inhibitors.
AID172878Percent change in Na+ in fasted rats at the dose of 10 mg/kg (iv), 0-5 h1990Journal of medicinal chemistry, Jun, Volume: 33, Issue:6
Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives.
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).
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]
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).
AID232283Saluretic activity in rats after 0-5 hours, as ratio of Na+/K+ ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
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
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]
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).
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID1137234Diuretic activity in acute sodium loaded Wistar rat assessed as sodium level in urine at 50 mg/kg, po measured for 0 to 5 hrs post drug dosing by flame photometer relative to urea1978Journal of medicinal chemistry, Apr, Volume: 21, Issue:4
Spiro[isobenzofuran-1(3H),4'-piperidines]. 3. Diuretic and antihypertensive properties of compounds containing a sulfur attached to nitrogen.
AID567091Drug absorption in human assessed as human intestinal absorption rate2011European journal of medicinal chemistry, Jan, Volume: 46, Issue:1
Prediction of drug intestinal absorption by new linear and non-linear QSPR.
AID172886Percent change in Na+in fasted rats at the dose of 30 mg/kg (po), 0-5 h1990Journal of medicinal chemistry, Jun, Volume: 33, Issue:6
Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives.
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).
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID28681Partition coefficient (logD6.5)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID173246Percent change in urinary volume in fasted rats at the dose of 30 mg/kg (po), 0-5 h1990Journal of medicinal chemistry, Jun, Volume: 33, Issue:6
Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives.
AID1123563Diuretic activity in Wistar rat assessed as sodium level in excreted urine at 50 mg/kg, po measured after 0 to 5 hrs by flame photometric analysis relative to urea-treated control1979Journal of medicinal chemistry, Jan, Volume: 22, Issue:1
Synthesis and evaluation for diuretic activity of 1-substituted 6-chloro-5-sulfamylindolines.
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID476929Human intestinal absorption in po dosed human2010European journal of medicinal chemistry, Mar, Volume: 45, Issue:3
Neural computational prediction of oral drug absorption based on CODES 2D descriptors.
AID1542240Permeability of the compound at 30 to 50 uM at pH 7.4 measured up to 6 hrs by PAMPA-BBB assay method2019European journal of medicinal chemistry, Apr-01, Volume: 167Tackling neuroinflammation and cholinergic deficit in Alzheimer's disease: Multi-target inhibitors of cholinesterases, cyclooxygenase-2 and 15-lipoxygenase.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID175819Diuretic activity in rats at time intervals of 5-24 hours1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
AID592684Apparent permeability of the compound by PAMPA2011Journal of medicinal chemistry, Apr-14, Volume: 54, Issue:7
In vitro characterization of human peptide transporter hPEPT1 interactions and passive permeation studies of short cationic antimicrobial peptides.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID1123565Diuretic activity in Wistar rat assessed as volume of excreted urine at 50 mg/kg, po measured after 5 to 24 hrs relative to urea-treated control1979Journal of medicinal chemistry, Jan, Volume: 22, Issue:1
Synthesis and evaluation for diuretic activity of 1-substituted 6-chloro-5-sulfamylindolines.
AID1123566Diuretic activity in Wistar rat assessed as sodium level in excreted urine at 50 mg/kg, po measured after 5 to 24 hrs by flame photometric analysis relative to urea-treated control1979Journal of medicinal chemistry, Jan, Volume: 22, Issue:1
Synthesis and evaluation for diuretic activity of 1-substituted 6-chloro-5-sulfamylindolines.
AID190283Saluretic activity in rats after 0-24 hours, as chloride ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
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.
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).
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.
AID604744Displacement of radiolabeled dansylsarcosine from fatty acid containing human serum albumin site 2 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID173243Percent change in urinary volume in fasted rats at the dose of 10 mg/kg (iv), 0-5 h1990Journal of medicinal chemistry, Jun, Volume: 33, Issue:6
Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives.
AID190284Saluretic activity in rats after 0-24 hours, as potassium ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
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).
AID455986Permeability across human Caco-2 cells2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Computational modeling of novel inhibitors targeting the Akt pleckstrin homology domain.
AID681388TP_TRANSPORTER: inhibition of PAH uptake in Xenopus laevis oocytes2000The Journal of pharmacology and experimental therapeutics, Oct, Volume: 295, Issue:1
Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1.
AID521220Inhibition of neurosphere proliferation of mouse neural precursor cells by MTT assay2007Nature chemical biology, May, Volume: 3, Issue:5
Chemical genetics reveals a complex functional ground state of neural stem cells.
AID27167Delta logD (logD6.5 - logD7.4)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID1150368Diuretic activity in po dosed albino Wistar-TNO rat assessed as 100% increase in urinary volume measured for 5 hrs1976Journal of medicinal chemistry, Jul, Volume: 19, Issue:7
A new class of diuretics with the 1,4-dioxino(2,3-g)quinolone structure.
AID1123567Diuretic activity in Wistar rat assessed as potassium level in excreted urine at 50 mg/kg, po measured after 5 to 24 hrs by flame photometric analysis relative to urea-treated control1979Journal of medicinal chemistry, Jan, Volume: 22, Issue:1
Synthesis and evaluation for diuretic activity of 1-substituted 6-chloro-5-sulfamylindolines.
AID190290Saluretic activity in rats after 5-24 hours, as potassium ion concentration in urine1986Journal of medicinal chemistry, Jun, Volume: 29, Issue:6
Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones.
AID604742Displacement of radiolabeled dansylsarcosine from fatty acid-free human serum albumin site 2 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID1794808Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL).2014Journal of biomolecular screening, Jul, Volume: 19, Issue:6
A High-Throughput Assay to Identify Inhibitors of the Apicoplast DNA Polymerase from Plasmodium falciparum.
AID1794808Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL).
AID588519A screen for compounds that inhibit viral RNA polymerase binding and polymerization activities2011Antiviral research, Sep, Volume: 91, Issue:3
High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors.
AID540299A screen for compounds that inhibit the MenB enzyme of Mycobacterium tuberculosis2010Bioorganic & medicinal chemistry letters, Nov-01, Volume: 20, Issue:21
Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: novel antibacterial agents against Mycobacterium tuberculosis.
AID588378qHTS for Inhibitors of ATXN expression: Validation
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.
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.
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.
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.
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.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
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.
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.
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.
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.
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.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS 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.
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.
AID1159550Human Phosphogluconate dehydrogenase (6PGD) Inhibitor Screening2015Nature cell biology, Nov, Volume: 17, Issue:11
6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (2,251)

TimeframeStudies, This Drug (%)All Drugs %
pre-19902077 (92.27)18.7374
1990's57 (2.53)18.2507
2000's39 (1.73)29.6817
2010's61 (2.71)24.3611
2020's17 (0.76)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 111.09

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 very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index111.09 (24.57)
Research Supply Index7.81 (2.92)
Research Growth Index4.45 (4.65)
Search Engine Demand Index207.65 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (111.09)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials78 (3.26%)5.53%
Reviews72 (3.01%)6.00%
Case Studies79 (3.31%)4.05%
Observational0 (0.00%)0.25%
Other2,160 (90.41%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (8)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure [NCT02546583]Phase 1458 participants (Actual)Interventional2015-08-31Completed
Prospective Comparison of Metolazone Versus Chlorothiazide for Acute Decompensated Heart Failure With Diuretic Resistance [NCT03574857]Phase 45 participants (Actual)Interventional2018-06-01Terminated(stopped due to Low enrollment)
Association Between Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use and COVID-19 Severity and Mortality Among US Veterans [NCT04467931]22,213 participants (Actual)Observational2020-01-19Completed
[NCT00004360]0 participants Observational1995-09-30Completed
Efficacy and Tolerability of Combination Intravenous Diuretic Therapy Versus Intravenous Loop Diuretic Therapy Alone for the Treatment of Acute Decompensated Heart Failure [NCT05840536]Phase 40 participants (Actual)Interventional2014-05-31Withdrawn
[NCT00000484]Phase 30 participants Interventional1966-04-30Completed
The CORONAvirus Disease 2019 Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker InvestigatiON (CORONACION) Randomized Clinical Trial [NCT04330300]Phase 42,414 participants (Anticipated)Interventional2020-04-30Suspended(stopped due to Challenges with funding and very low incidence of COVID-19 at Irish study site)
Comparison of Oral Thiazides vs Intravenous Thiazides vs Tolvaptan in Combination With Loop Diuretics for Diuretic Resistant Decompensated Heart Failure [NCT02606253]Phase 460 participants (Actual)Interventional2016-02-29Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT02606253 (18) [back to overview]Change in eGFR From Baseline to 48 Hours
NCT02606253 (18) [back to overview]Change in Patient Congestion Score
NCT02606253 (18) [back to overview]Change in Serum Chloride From Baseline
NCT02606253 (18) [back to overview]Diuretic Efficiency
NCT02606253 (18) [back to overview]Mean Change in Glomerular Filtration Rate at Discharge
NCT02606253 (18) [back to overview]Mean Change in Serum Creatinine
NCT02606253 (18) [back to overview]Mean Change in Serum Potassium
NCT02606253 (18) [back to overview]Mean Change in Serum Sodium
NCT02606253 (18) [back to overview]Net Urine Output
NCT02606253 (18) [back to overview]Number of Patients With Cardiac Arrhythmias
NCT02606253 (18) [back to overview]Number of Patients With Escalation of Loop Diuretic Therapy
NCT02606253 (18) [back to overview]Number of Patients With Hypokalemia
NCT02606253 (18) [back to overview]Number of Patients With In-hospital Mortality
NCT02606253 (18) [back to overview]Number of Patients With New Inotrope Utilization
NCT02606253 (18) [back to overview]Number of Patients With Renal Replacement Therapy Utilization
NCT02606253 (18) [back to overview]Number of Patients With Symptomatic Hypotension
NCT02606253 (18) [back to overview]Potassium Supplementation
NCT02606253 (18) [back to overview]Weight Change Over 48 Hours

Change in eGFR From Baseline to 48 Hours

Change in estimated glomerular filtration rate (ml/min/m2) from baseline to 48 hours (NCT02606253)
Timeframe: 48 hours

Interventionml/min/m2 (Mean)
Metolazone-6
Chlorothiazide-9
Tolvaptan2

[back to top]

Change in Patient Congestion Score

"Participants will score their congestion on a 10cm scale ranging from Best (10cm) to Worst (0cm). Change in score (units in centimeters) from baseline to 48 hours." (NCT02606253)
Timeframe: 48 hours

Interventioncm of dyspena analog scale (Median)
Metolazone4.0
Chlorothiazide3.0
Tolvaptan3.0

[back to top]

Change in Serum Chloride From Baseline

Change in serum chloride (mEq/L) from baseline to 48 hrs (NCT02606253)
Timeframe: 48 hours

InterventionmEq/L (Mean)
Metolazone-7
Chlorothiazide-7
Tolvaptan2

[back to top]

Diuretic Efficiency

Diuretic Efficiency is calculated as 48hr urine output/ 48hr Furosemide equivalents in milligrams (NCT02606253)
Timeframe: 48 hours

InterventionUOP / 40mg IV furosemide (Mean)
Metolazone217
Chlorothiazide294
Tolvaptan326

[back to top]

Mean Change in Glomerular Filtration Rate at Discharge

Mean change in glomerular filtration rate from enrollment to end of study at hospital discharge, an average of 5 days (NCT02606253)
Timeframe: hospital discharge an average of 5 days

Interventionml/min/m2 (Mean)
Metolazone-2
Chlorothiazide-2
Tolvaptan-6

[back to top]

Mean Change in Serum Creatinine

Mean change in serum creatinine (mg/dl) from enrollment to end of study at 48 hours (NCT02606253)
Timeframe: 48 hours

Interventionmg/dl (Mean)
Metolazone0.3
Chlorothiazide0.5
Tolvaptan0.03

[back to top]

Mean Change in Serum Potassium

Mean change in serum potassium (mEq/L) from enrollment to end of study at 48 hours (NCT02606253)
Timeframe: 48 hours

InterventionmEq/L (Mean)
Metolazone-0.1
Chlorothiazide-0.2
Tolvaptan0.1

[back to top]

Mean Change in Serum Sodium

Mean change in serum sodium (mEq/L) from enrollment to end of study at 48 hours (NCT02606253)
Timeframe: 48 hours

InterventionmEq/L (Mean)
Metolazone-1
Chlorothiazide-1
Tolvaptan4

[back to top]

Net Urine Output

Net urine output from enrollment to the end of study at 48 hours measured in liters (NCT02606253)
Timeframe: 48 hours

Interventionliters (Median)
Metolazone-7.8
Chlorothiazide-8.8
Tolvaptan-9.8

[back to top]

Number of Patients With Cardiac Arrhythmias

Incidence of new atrial or ventricular arrhythmias from enrollment to end of study at 48 hours (NCT02606253)
Timeframe: 48 hours

InterventionParticipants (Count of Participants)
Metolazone0
Chlorothiazide0
Tolvaptan0

[back to top]

Number of Patients With Escalation of Loop Diuretic Therapy

Provider escalation of loop diuretic dosage at 24 hours for urine output less than 3 L at 24 hours (NCT02606253)
Timeframe: 24 hours

InterventionParticipants (Count of Participants)
Metolazone4
Chlorothiazide4
Tolvaptan2

[back to top]

Number of Patients With Hypokalemia

Incidence of hypokalemia (serum potassium less than 3.5mEq/L ) from enrollment to end of study (NCT02606253)
Timeframe: 48 hours

InterventionParticipants (Count of Participants)
Metolazone3
Chlorothiazide2
Tolvaptan2

[back to top]

Number of Patients With In-hospital Mortality

Incidence of death from study enrollment to hospital discharge, an average of 5 days (NCT02606253)
Timeframe: Enrollment to hospital discharge an average of 5 days

InterventionParticipants (Count of Participants)
Metolazone0
Chlorothiazide0
Tolvaptan0

[back to top]

Number of Patients With New Inotrope Utilization

Incidence of new initiation of dopamine, dobutamine, or milrinone from enrollment to end of study at 48 hours (NCT02606253)
Timeframe: 48 hours

InterventionParticipants (Count of Participants)
Metolazone1
Chlorothiazide0
Tolvaptan2

[back to top]

Number of Patients With Renal Replacement Therapy Utilization

Incidence of Renal replacement therapy utilization (hemodialysis, ultrafiltration) from enrollment to hospital discharge, an average of 5 days (NCT02606253)
Timeframe: enrollment to hospital discharge an average of 5 days

InterventionParticipants (Count of Participants)
Metolazone0
Chlorothiazide0
Tolvaptan0

[back to top]

Number of Patients With Symptomatic Hypotension

SBP < 85 mmHg plus medical intervention for symptomatic hypotension (NCT02606253)
Timeframe: 48 hours

InterventionParticipants (Count of Participants)
Metolazone2
Chlorothiazide0
Tolvaptan2

[back to top]

Potassium Supplementation

Cumulative dose of potassium supplementation (mEq) administered from enrollment to end of study at 48 hours (NCT02606253)
Timeframe: 48 hours

InterventionmEq (Mean)
Metolazone103
Chlorothiazide63
Tolvaptan58

[back to top]

Weight Change Over 48 Hours

The primary outcome will be 48-hour standing scale weight change (kg) from enrollment among the metolazone, intravenous chlorothiazide, and tolvaptan arms, using metolazone group as the comparator group for all other groups. (NCT02606253)
Timeframe: 48 hours

Interventionkg (Mean)
Metolazone-4.6
Chlorothiazide-5.8
Tolvaptan-4.1

[back to top]