Troglitazone

Summary

Troglitazone (CHEMBL408) is an approved small-molecule hypoglycemic agent (ATC A10BG01) targeting TRPM3 and PPARG; indicated across 2 conditions including diabetes mellitus and sarcoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A10BG01
• Targets: 2 (TRPM3, PPARG)
• Indications: 2 conditions
• Clinical trials: 2
• Chemistry: C24H27NO5S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL408
Name	Troglitazone
Type	Small molecule
Max phase	4
ChEBI	CHEBI:9753
ATC	A10BG01
Molecular formula	C24H27NO5S
InChIKey	GXPHKUHSUJUWKP-UHFFFAOYSA-N

SMILES: Cc1c(C)c2c(c(C)c1O)CCC(C)(COc1ccc(CC3SC(=O)NC3=O)cc1)O2

Pharmacological roles (ChEBI): hypoglycemic agent, antioxidant, vasodilator agent, anticonvulsant, anticoagulant, platelet aggregation inhibitor, antineoplastic agent, EC 6.2.1.3 (long-chain-fatty-acid—CoA ligase) inhibitor, ferroptosis inhibitor.

Also known as: CI-991, CS-045, GR-92132X, GR92132X, Prelay, Rezulin, Romozin, Troglitazona, Troglitazone, troglitazone, SID26755242, SID26755243

Patent coverage: 10,055 distinct patent families (38,856 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 38,756 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
TRPM3	TRPM3			0.1%	Q9HCF6
PPARG	Peroxisome proliferator-activated receptor-γ	Full agonist	5.8	2.6%	P37231

Broader ChEMBL bioactivity targets: 63 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Indoleamine 2,3-dioxygenase 1, Microtubule-associated protein tau, Nuclear receptor ROR-gamma, ATP-dependent DNA helicase Q1, ATP-binding cassette sub-family C member 4, UDP-glucuronosyltransferase 1A6, 5-hydroxytryptamine receptor 2B, Thromboxane-A synthase, Alpha-2A adrenergic receptor.

Bioactivity

ChEMBL activities: 85 potent at pChembl ≥ 5 of 130 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
FOXM1	7.28	Ki	51.97	nM	CHEMBL_ACT_22907721
PPARG	6.7	Ki	200	nM	CHEMBL_ACT_24751890
PPARG	6.67	EC50	215	nM	CHEMBL_ACT_18854505
PPARG	6.55	AC50	283.9	nM	CHEMBL_ACT_25114135
PPARG	6.52	IC50	300	nM	CHEMBL_ACT_10896501
PPARG	6.52	Ki	302	nM	CHEMBL_ACT_243259
PPARG	6.52	Ki	302	nM	CHEMBL_ACT_542470
PPARG	6.47	IC50	340	nM	CHEMBL_ACT_15657621
PPARG	6.47	EC50	340	nM	CHEMBL_ACT_26140315
PPARG	6.43	IC50	370	nM	CHEMBL_ACT_18758355
PPARG	6.42	Ki	380	nM	CHEMBL_ACT_18494907
PPARG	6.4	EC50	400	nM	CHEMBL_ACT_10896423
PPARG	6.4	EC50	400	nM	CHEMBL_ACT_12045140
PPARG	6.4	Ki	400	nM	CHEMBL_ACT_22424949
PPARG	6.36	EC50	440	nM	CHEMBL_ACT_10899114
PPARG	6.36	EC50	440	nM	CHEMBL_ACT_8059810
PPARG	6.27	EC50	537	nM	CHEMBL_ACT_243260
PPARG	6.27	EC50	537	nM	CHEMBL_ACT_542471
PPARG	6.26	EC50	550	nM	CHEMBL_ACT_513986
PPARG	6.14	EC50	730	nM	CHEMBL_ACT_10833281
PPARG	6.14	EC50	720	nM	CHEMBL_ACT_12066451
P37238	6.11	EC50	780	nM	CHEMBL_ACT_513983
O35505	6.1	IC50	800	nM	CHEMBL_ACT_15777560
HTR2B	6.08	Ki	835	nM	CHEMBL_ACT_7790736
CA2	6.01	IC50	970	nM	CHEMBL_ACT_7788965
PPARG	6.01	EC50	980	nM	CHEMBL_ACT_964126
PPARG	6	EC50	1000	nM	CHEMBL_ACT_13403379
P37238	6	EC50	1000	nM	CHEMBL_ACT_6197530
MAPK1	5.91	IC50	1238	nM	CHEMBL_ACT_7790711
PPARG	5.89	IC50	1285	nM	CHEMBL_ACT_1038634

Target pathways

Aggregated over 2 target gene(s): TRPM3, PPARG.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
PPARA activates gene expression	1	PPARG
TRP channels	1	TRPM3
Transcriptional regulation of white adipocyte differentiation	1	PPARG
Nuclear Receptor transcription pathway	1	PPARG
SUMOylation of intracellular receptors	1	PPARG
Regulation of PTEN gene transcription	1	PPARG
MECP2 regulates transcription factors	1	PPARG
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	PPARG
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	PPARG

Dominant GO biological processes

GO term	Targets
monoatomic cation transport	1
calcium ion transport	1
protein homotetramerization	1
calcium ion transmembrane transport	1
zinc ion transmembrane transport	1
monoatomic cation transmembrane transport	1
monoatomic ion transport	1
monoatomic ion transmembrane transport	1
protein tetramerization	1
transmembrane transport	1
negative regulation of transcription by RNA polymerase II	1
placenta development	1
regulation of transcription by RNA polymerase II	1
fatty acid metabolic process	1
response to nutrient	1

Indications & clinical

Indications

2 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
diabetes mellitus	4	MONDO:0005015	EFO:0000400
sarcoma	2	MONDO:0005089	EFO:0000691

Clinical trials

Total trials: 2.

Phase distribution

Phase	Trials
PHASE2/PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00116545	PHASE2/PHASE3	COMPLETED	TART - Troglitazone Atherosclerosis Regression Trial
NCT00003058	PHASE2	COMPLETED	Troglitazone in Treating Patients With Liposarcoma

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

84 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Pioglitazone	ChEMBL + PubChem	Phase 4 (approved)	PPARG, TRPM3
Rosiglitazone	ChEMBL + PubChem	Phase 4 (approved)	PPARG, TRPM3
FULVESTRANT	ChEMBL + PubChem	Phase 4 (approved)	PPARG
BENZBROMARONE	ChEMBL	Phase 4 (approved)	PPARG
BEXAROTENE	ChEMBL	Phase 4 (approved)	PPARG
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	PPARG
CANNABIDIOL	ChEMBL	Phase 4 (approved)	PPARG
CARVEDILOL	ChEMBL	Phase 4 (approved)	PPARG
CEFAMANDOLE	ChEMBL	Phase 4 (approved)	PPARG
CEFOTAXIME	ChEMBL	Phase 4 (approved)	PPARG
CEFOXITIN	ChEMBL	Phase 4 (approved)	PPARG
CEFTAZIDIME	ChEMBL	Phase 4 (approved)	PPARG
CEFTRIAXONE	ChEMBL	Phase 4 (approved)	PPARG
CLOBETASOL PROPIONATE	ChEMBL	Phase 4 (approved)	PPARG
EFAVIRENZ	ChEMBL	Phase 4 (approved)	PPARG
ELAFIBRANOR	ChEMBL	Phase 4 (approved)	PPARG
FENOFIBRATE	ChEMBL	Phase 4 (approved)	PPARG
FENOFIBRIC ACID	ChEMBL	Phase 4 (approved)	PPARG
GEMFIBROZIL	ChEMBL	Phase 4 (approved)	PPARG
GLYBURIDE	ChEMBL	Phase 4 (approved)	PPARG
INDOMETHACIN	ChEMBL	Phase 4 (approved)	PPARG
LASOFOXIFENE	ChEMBL	Phase 4 (approved)	PPARG
LEVOTHYROXINE	ChEMBL	Phase 4 (approved)	PPARG
LIOTHYRONINE	ChEMBL	Phase 4 (approved)	PPARG
LUMIRACOXIB	ChEMBL	Phase 4 (approved)	PPARG
MASOPROCOL	ChEMBL	Phase 4 (approved)	PPARG
METHYLENE BLUE	ChEMBL	Phase 4 (approved)	PPARG
MONTELUKAST	ChEMBL	Phase 4 (approved)	PPARG
NINTEDANIB	ChEMBL	Phase 4 (approved)	PPARG
PEMAFIBRATE	ChEMBL	Phase 4 (approved)	PPARG
RIMONABANT	ChEMBL	Phase 4 (approved)	PPARG
SULINDAC	ChEMBL	Phase 4 (approved)	PPARG
TELMISARTAN	ChEMBL	Phase 4 (approved)	PPARG
TERIFLUNOMIDE	ChEMBL	Phase 4 (approved)	PPARG
TIPRANAVIR	ChEMBL	Phase 4 (approved)	PPARG
ZAFIRLUKAST	ChEMBL	Phase 4 (approved)	PPARG
ALEGLITAZAR	ChEMBL	Phase 3	PPARG
BALAGLITAZONE	ChEMBL	Phase 3	PPARG
BEZAFIBRATE	ChEMBL	Phase 3	PPARG
CANDESARTAN	ChEMBL	Phase 3	PPARG
DOCONEXENT	ChEMBL	Phase 3	PPARG
GAMOLENIC ACID	ChEMBL	Phase 3	PPARG
ICOSAPENT	ChEMBL	Phase 3	PPARG
IMIGLITAZAR	ChEMBL	Phase 3	PPARG
LANIFIBRANOR	ChEMBL	Phase 3	PPARG
LERIGLITAZONE	ChEMBL	Phase 3	PPARG
LOBEGLITAZONE	ChEMBL	Phase 3	PPARG
MURAGLITAZAR	ChEMBL	Phase 3	PPARG
NAMODENOSON	ChEMBL	Phase 3	PPARG
QUERCETIN	ChEMBL	Phase 3	PPARG
RESVERATROL	ChEMBL	Phase 3	PPARG
RIVOGLITAZONE	ChEMBL	Phase 3	PPARG
TESAGLITAZAR	ChEMBL	Phase 3	PPARG
TIRATRICOL	ChEMBL	Phase 3	PPARG
ARHALOFENATE	ChEMBL	Phase 2	PPARG
ATX08-001	ChEMBL	Phase 2	PPARG
CANNABIGEROL	ChEMBL	Phase 2	PPARG
CIGLITAZONE	ChEMBL	Phase 2	PPARG
CXA-10	ChEMBL	Phase 2	PPARG
DIHOMO-GAMMA-LINOLENIC ACID	ChEMBL	Phase 2	PPARG