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 This drug was withdrawn from the UK market due to liver toxicity.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
780.0 nM [EC50]
Target ID: P18146
Gene ID: 1958.0
Gene Symbol: EGR1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
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

8.5449599E11
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Troglitazone, a PPARgamma ligand, inhibits osteopontin gene expression in human monocytes/macrophage THP-1 cells.
2000
Differential activation of peroxisome proliferator-activated receptor-gamma by troglitazone and rosiglitazone.
2000 Apr
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
Vitamin K(2) inhibits adipogenesis, osteoclastogenesis, and ODF/RANK ligand expression in murine bone marrow cell cultures.
2000 Dec
Down-regulation by troglitazone of hepatic tumor necrosis factor-alpha and interleukin-6 mRNA expression in a murine model of non-insulin-dependent diabetes.
2000 Jul 1
Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets.
2000 Jul 18
Inhibitory effect of troglitazone on TNF-alpha-induced expression of monocyte chemoattractant protein-1 (MCP-1) in human endothelial cells.
2000 Jun
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
Troglitazone-induced fulminant hepatitis: report of a case with autopsy findings.
2000 May-Jun
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
Troglitazone induces apoptosis via the p53 and Gadd45 pathway in vascular smooth muscle cells.
2000 Nov 3
Activation of peroxisome proliferator-activated receptor gamma by troglitazone inhibits cell growth through the increase of p27KiP1 in human. Pancreatic carcinoma cells.
2000 Oct 1
Down-regulation of uncoupling protein-3 and -2 by thiazolidinediones in C2C12 myotubes.
2000 Oct 27
Two opposing effects of non-steroidal anti-inflammatory drugs on the expression of the inducible cyclooxygenase. Mediation through different signaling pathways.
2000 Sep 8
Effects of type-2 diabetes and troglitazone on the expression patterns of small intestinal sugar transporters and PPAR-gamma in the Zucker diabetic fatty rat.
2001
Peroxisome proliferator-activated receptor gamma ligands suppress the transcriptional activation of cyclooxygenase-2. Evidence for involvement of activator protein-1 and CREB-binding protein/p300.
2001 Apr 13
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
Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: pleiotropic effects on CD36 expression and HDL.
2001 Mar
Severe cholestatic hepatitis from troglitazone in a patient with nonalcoholic steatohepatitis and diabetes mellitus.
2001 May
Involvement of p21(WAF1/Cip1), p27(Kip1), and p18(INK4c) in troglitazone-induced cell-cycle arrest in human hepatoma cell lines.
2001 May
Troglitazone induces GLUT4 translocation in L6 myotubes.
2001 May
Inhibition of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by troglitazone: a peroxisome proliferator-activated receptor-gamma (PPARgamma)-independent, antioxidant-related mechanism.
2001 Oct 15
Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate.
2001 Oct 5
Regulation of the glyoxalase pathway in human brain microvascular endothelium: effects of troglitazone and tertiary butylhydroperoxide.
2002
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
Troglitazone suppresses the secretion of type I collagen by mesangial cells in vitro.
2002 Apr
Thiazolidinedione derivatives ameliorate albuminuria in streptozotocin-induced diabetic spontaneous hypertensive rat.
2002 Apr
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation suppresses ischemic induction of Egr-1 and its inflammatory gene targets.
2002 Dec
Receptor-dependent regulation of the CYP3A4 gene.
2002 Dec 27
Unique ability of troglitazone to up-regulate peroxisome proliferator-activated receptor-gamma expression in hepatocytes.
2002 Jan
Growth inhibition and differentiation of pancreatic cancer cell lines by PPAR gamma ligand troglitazone.
2002 Jan
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.
2002 Jan 11
Troglitazone induces G1 arrest by p27(Kip1) induction that is mediated by inhibition of proteasome in human gastric cancer cells.
2002 Jul
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
Troglitazone, an insulin-sensitizing thiazolidinedione, represses combined stimulation by LH and insulin of de novo androgen biosynthesis by thecal cells in vitro.
2002 Mar
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
Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition.
2003 Apr
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 but not rosiglitazone induces G1 cell cycle arrest and apoptosis in human and rat hepatoma cell lines.
2003 Mar 20
A cohort study of the incidence of serious acute liver injury in diabetic patients treated with hypoglycemic agents.
2003 Mar 24
Patents

Sample Use Guides

Prelay (TROGLITAZONE tablet) should be taken with a meal. Combination Therapy: Sulfonylureas: Prelay in combination with a sulfonylurea should be initiated at 200 mg once daily. The current sulfonylurea dose should be continued upon initiation of Prelay therapy. For patients not responding adequately, the Rezulin dose should be increased at 2 to 4 weeks. The maximum recommended dose is 600 mg once daily. The dose of sulfonylurea may require lowering to optimize therapy. Metformin: For patients not responding adequately to metformin and sulfonylurea therapy, 400 mg daily of Prelay may be added. Insulin: The current insulin dose should be continued upon initiation of Prelay therapy. Prelay therapy should be initiated at 200 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of Prelay should be increased after approximately 2 to 4 weeks. The usual dose of Prelay is 400 mg once daily. The maximum recommended daily dose is 600 mg. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and Prelay. Further adjustments should be individualized based on glucose-lowering response. Patients With Renal Insufficiency: Dose adjustment in patients with renal insufficiency is not required
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
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Biological Half-life PHARMACOKINETIC
Definition References