U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
Troglitazone (TGZ, brand name: Rezulin and Prelay) is a peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, which was developed by Daiichi Sankyo and approved for the US market for the treatment of Type II diabetes mellitus. The drug is used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise, and was not indicated as initial therapy in patients with type 2 diabetes. This drug was withdrawn from the UK market due to liver toxicity. It was removed from the US market in 2000, only 3 years after its introduction and from Japan, shortly afterward. In addition, was conducted a clinical trial for the treatment of patients with advanced liposarcoma by using troglitazone, but the positive result wasn’t obtained. It was shown, that in case of cancer cells troglitazone acted independently of PPAR gamma, by up-regulation of early growth response-1 (Egr-1). Egr-1 transcription factor has been linked to apoptosis and shown to be activated by extracellular signal-regulated kinase (ERK).

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
780 nM [EC50]
Target ID: P18146
Gene ID: 1958
Gene Symbol: EGR1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Palliative
PRELAY

Approved Use

Prelay is indicated to improve glycemic control in patients with type 2 diabetes mellitus as an adjunct to diet and exercise in combination with (not substituted for): · A sulfonylurea drug for patients who are not adequately controlled with a sulfonylurea alone or, · A sulfonylurea drug together with metformin for patients who are not adequately controlled with the combination of a sulfonylurea and metformin or, · Insulin in patients who are not adequately controlled with insulin alone. Prelay is not indicated as initial therapy in patients with type 2 diabetes

Launch Date

854496000000
Primary
PubMed

PubMed

TitleDatePubMed
p53 is not inactivated in B6C3F1 mouse vascular tumors arising spontaneously or associated with long-term administration of the thiazolidinedione troglitazone.
1999 Apr 15
Troglitazone suppresses cell growth of myeloid leukemia cell lines by induction of p21WAF1/CIP1 cyclin-dependent kinase inhibitor.
1999 Aug 11
Troglitazone-associated hepatic failure.
1999 Feb 16
Vasodilatory effects of troglitazone improve blood pressure at rest and during mental stress in type 2 diabetes mellitus.
1999 Jul
Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma.
1999 Mar 30
Growth inhibition of myeloid leukemia cells by troglitazone, a ligand for peroxisome proliferator activated receptor gamma, and retinoids.
1999 Nov
Chemoprevention of heterocyclic amine-induced carcinogenesis by phenolic compounds in rats.
1999 Sep 1
Troglitazone induces expression of PPARgamma in liver.
1999 Sep-Dec
Stimulation by eicosapentaenoic acids of leptin mRNA expression and its secretion in mouse 3T3-L1 adipocytes in vitro.
2000 Apr 13
Leptin production in adipocytes from morbidly obese subjects: stimulation by dexamethasone, inhibition with troglitazone, and influence of gender.
2000 Aug
Dehydroepiandrosterone suppresses elevated hepatic glucose-6-phosphatase mRNA level in C57BL/KsJ-db/db mice: comparison with troglitazone.
2000 Dec
Enhancing effect of troglitazone on porcine adipocyte differentiation in primary culture: a comparison with dexamethasone.
2000 Dec
Characterization of UDP-glucuronosyltransferases (UGTS) involved in the metabolism of troglitazone in rats and humans.
2000 Dec
Troglitazone halts diabetic glomerulosclerosis by blockade of mesangial expansion.
2000 Dec
Inhibitory effect of troglitazone on tumor necrosis factor alpha-induced expression of monocyte chemoattractant protein-1 in human mesangial cells.
2000 Feb
Subacute hepatic failure associated with a new antidiabetic agent, troglitazone: a case report with autopsy examination.
2000 Feb
Peroxisome proliferator-activated receptor (PPAR)-gamma expression in human vascular smooth muscle cells: inhibition of growth, migration, and c-fos expression by the peroxisome proliferator-activated receptor (PPAR)-gamma activator troglitazone.
2000 Jan
Impaired expression of the uncoupling protein-3 gene in skeletal muscle during lactation: fibrates and troglitazone reverse lactation-induced downregulation of the uncoupling protein-3 gene.
2000 Jul
Troglitazone reduces plasminogen activator inhibitor-1 expression and secretion in cultured human adipocytes.
2000 Mar
Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-gamma inhibit keratinocyte proliferation.
2000 May
Troglitazone inhibits mitogenic signaling by insulin in vascular smooth muscle cells.
2000 May
Insulin sensitizer, troglitazone, directly inhibits aromatase activity in human ovarian granulosa cells.
2000 May 19
Regulation of leptin release by troglitazone in human adipose tissue.
2000 Nov
Up-regulation of peroxisome proliferator-activated receptors (PPAR-alpha) and PPAR-gamma messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-gamma-responsive adipose tissue-specific genes in the liver of obese diabetic mice.
2000 Nov
Down-regulation of uncoupling protein-3 and -2 by thiazolidinediones in C2C12 myotubes.
2000 Oct 27
15-Deoxy-delta 12,14-prostaglandin J2 and thiazolidinediones activate the MEK/ERK pathway through phosphatidylinositol 3-kinase in vascular smooth muscle cells.
2001 Dec 28
Failure to develop hepatic injury from rosiglitazone in a patient with a history of troglitazone-induced hepatitis.
2001 Jan
Abundant expression of uncoupling protein-2 in the small intestine: up-regulation by dietary fish oil and fibrates.
2001 Jan 15
Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action?
2001 Jul
Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: pleiotropic effects on CD36 expression and HDL.
2001 Mar
Enzymatic characterization and interspecies difference of phenol sulfotransferases, ST1A forms.
2001 Mar
Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: in vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat.
2001 Mar
Bezafibrate attenuates the overexpression of plasminogen activator inhibitor-1 messenger RNA by a combination of mono-unsaturated fatty acid and insulin in hepG2 cells.
2001 Mar 9
Troglitazone treatment increases plasma vascular endothelial growth factor in diabetic patients and its mRNA in 3T3-L1 adipocytes.
2001 May
Peroxisome proliferator-activated receptor-gamma agonist troglitazone protects against nondiabetic glomerulosclerosis in rats.
2001 May
Concentration-dependent stimulatory and inhibitory effect of troglitazone on insulin-induced fatty acid synthase expression and protein kinase B activity in 3T3-L1 adipocytes.
2002 Apr
Receptor-dependent regulation of the CYP3A4 gene.
2002 Dec 27
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.
2002 Jan 11
Nonsteroidal anti-inflammatory drugs induce apoptosis in association with activation of peroxisome proliferator-activated receptor gamma in rheumatoid synovial cells.
2002 Jul
Troglitazone improves GLUT4 expression in adipose tissue in an animal model of obese type 2 diabetes mellitus.
2002 Jun
Effects of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (p,p'-DDT) on 3T3-L1 and 3T3-F442A adipocyte differentiation.
2002 Mar 1
Troglitazone activates p21Cip/WAF1 through the ERK pathway in HCT15 human colorectal cancer cells.
2002 May 28
The effects of troglitazone, an insulin-sensitizing agent, on the endothelial function in early and late type 2 diabetes: a placebo-controlled randomized clinical trial.
2003 Feb
Troglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma ) ligand, selectively induces the early growth response-1 gene independently of PPAR gamma. A novel mechanism for its anti-tumorigenic activity.
2003 Feb 21
Troglitazone but not rosiglitazone induces G1 cell cycle arrest and apoptosis in human and rat hepatoma cell lines.
2003 Mar 20
Patents

Sample Use Guides

Prelay (TROGLITAZONE tablet) should be taken with a meal.
Route of Administration: Oral
Human HCC cell lines Huh7 and Hep3B were cultured in the presence or absence of troglitazone. Cell growth was determined via WST-1 assay, proliferation by cell cycle analysis and proliferating cell nuclear antigen (PCNA) Western blotting, and apoptosis by flow cytometry and TUNEL. In cultures of Hep3B and Huh7 cells, basal expression of PPARgamma was relatively low, but troglitazone caused dose-dependent induction of PPARgamma expression.
Substance Class Mixture
Created
by admin
on Sat Jun 26 12:19:56 UTC 2021
Edited
by admin
on Sat Jun 26 12:19:56 UTC 2021
Record UNII
I66ZZ0ZN0E
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TROGLITAZONE
INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
TROGLITAZONE [USAN]
Common Name English
TROGLITAZONE [JAN]
Common Name English
TROGLITAZONE [MI]
Common Name English
CS-045
Code English
TROGLITAZONE [MART.]
Common Name English
REZULIN
Brand Name English
TROGLITAZONE [VANDF]
Common Name English
PRELAY
Brand Name English
CI-991
Code English
2,4-THIAZOLIDINEDIONE, 5-((4-((3,4-DIHYDRO-6-HYDROXY-2,5,7,8-TETRAMETHYL-2H-1-BENZOPYRAN-2-YL)METHOXY)PHENYL)METHYL)-
Common Name English
TROGLITAZONE [INN]
Common Name English
TROGLITAZONE [WHO-DD]
Common Name English
GR92132X
Code English
GR-92132X
Code English
TROGLITAZONE [ORANGE BOOK]
Common Name English
(+/-)-ALL-RAC-5-(P-((6-HYDROXY-2,5,7,8-TETRAMETHYL-2-CHROMANYL)METHOXY)BENZYL)-2,4-THIAZOLIDINEDIONE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1934
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
WHO-ATC A10BG01
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
LIVERTOX 1008
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
WHO-VATC QA10BG01
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
NCI_THESAURUS C98241
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
Code System Code Type Description
EVMPD
SUB11332MIG
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
FDA UNII
I66ZZ0ZN0E
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
MERCK INDEX
M11218
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB00197
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
NCI_THESAURUS
C1522
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
ChEMBL
CHEMBL408
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
EPA CompTox
97322-87-7
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
MESH
C057693
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
WIKIPEDIA
TROGLITAZONE
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
PUBCHEM
5591
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
RXCUI
72610
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
2767
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
INN
6851
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
CAS
97322-87-7
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
IUPHAR
2693
Created by admin on Sat Jun 26 12:19:57 UTC 2021 , Edited by admin on Sat Jun 26 12:19:57 UTC 2021
PRIMARY
All of the following components must be present:
Related Record Type Details
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TRANSPORTER -> INHIBITOR
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TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> INDUCER
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BINDING
METABOLIC ENZYME -> INDUCER
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METABOLITE -> PARENT
MAJOR
FECAL; PLASMA; URINE
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Definition References