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Description

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 This drug was withdrawn from the UK market due to liver toxicity.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).

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Troglitazone, a PPARgamma ligand, inhibits osteopontin gene expression in human monocytes/macrophage THP-1 cells.
2000
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
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
Troglitazone, a ligand for peroxisome proliferator-activated receptor gamma, inhibits chemically-induced aberrant crypt foci in rats.
2001 Apr
Effect of obesity and troglitazone on expression of two glutathione peroxidases: cellular and extracellular types in serum, kidney and adipose tissue.
2001 Apr
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
Dual function of troglitazone in ICAM-1 gene expression in human vascular endothelium.
2001 Apr 6
Arylhydrocarbon receptor (AhR) is involved in negative regulation of adipose differentiation in 3T3-L1 cells: AhR inhibits adipose differentiation independently of dioxin.
2001 Aug
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
Myositis, microvesicular hepatitis, and progression to cirrhosis from troglitazone added to simvastatin.
2001 Feb
Troglitazone and rosiglitazone induce apoptosis of vascular smooth muscle cells through an extracellular signal-regulated kinase-independent pathway.
2001 Feb
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
15-Deoxy-delta12,14-PGJ2, but not troglitazone, modulates IL-1beta effects in human chondrocytes by inhibiting NF-kappaB and AP-1 activation pathways.
2001 Jul 13
Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: pleiotropic effects on CD36 expression and HDL.
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
Severe cholestatic hepatitis from troglitazone in a patient with nonalcoholic steatohepatitis and diabetes mellitus.
2001 May
Troglitazone induces GLUT4 translocation in L6 myotubes.
2001 May
Peroxisome proliferator-activated receptor-gamma agonist troglitazone protects against nondiabetic glomerulosclerosis in rats.
2001 May
Troglitazone improves endothelial function and augments renal klotho mRNA expression in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with multiple atherogenic risk factors.
2001 Nov
Troglitazone selectively inhibits glyoxalase I gene expression.
2001 Nov
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
Troglitazone downregulates delta-6 desaturase gene expression in human skeletal muscle cell cultures.
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
Troglitazone suppresses cell growth of KU812 cells independently of PPARgamma.
2002 Feb 1
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
PPAR gamma ligands, troglitazone and pioglitazone, up-regulate expression of HMG-CoA synthase and HMG-CoA reductase gene in THP-1 macrophages.
2002 Jun 5
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
Troglitazone treatment of aging Brown Norway rats improves food intake and weight gain after fasting without increasing hypothalamic NPY gene expression.
2002 May
Troglitazone activates p21Cip/WAF1 through the ERK pathway in HCT15 human colorectal cancer cells.
2002 May 28
Effects of leptin, troglitazone, and dietary fat on stearoyl CoA desaturase.
2002 Oct 11
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, 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
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

In Vivo Use Guide
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
In Vitro Use Guide
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 Tue Oct 22 00:11:59 UTC 2019
Edited
by admin
on Tue Oct 22 00:11:59 UTC 2019
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 Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
WHO-ATC A10BG01
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
LIVERTOX 1008
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
WHO-VATC QA10BG01
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
NCI_THESAURUS C98241
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
Code System Code Type Description
EVMPD
SUB11332MIG
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY
MERCK INDEX
M11218
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY Merck Index
NCI_THESAURUS
C1522
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY
ChEMBL
CHEMBL408
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY
EPA CompTox
97322-87-7
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY
MESH
C057693
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY
WIKIPEDIA
TROGLITAZONE
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY
RXCUI
72610
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY RxNorm
INN
6851
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY
CAS
97322-87-7
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY
IUPHAR
2693
Created by admin on Tue Oct 22 00:11:59 UTC 2019 , Edited by admin on Tue Oct 22 00:11:59 UTC 2019
PRIMARY
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Related Record Type Details
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TARGET -> AGONIST
METABOLIC ENZYME -> INDUCER
METABOLIC ENZYME -> INDUCER
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE -> PARENT
MAJOR
FECAL; PLASMA; URINE
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Definition References