Skip to main content
Free research Free research Free compound review with research home and workspace preview
Quick search ChEMBL 36
Compound Detail

CHEMBL408

TROGLITAZONE
💊 Approved Drug
Enter ChEMBL ID:
Free Research Context This compound will appear in recent viewed items on the research home for this browser.
Research home View demo workspace
💊 Approved Drug
Cc1c(C)c2c(c(C)c1O)CCC(C)(COc1ccc(CC3SC(=O)NC3=O)cc1)O2

Basic Information

ChEMBL ID CHEMBL408
Name TROGLITAZONE
Phase Approved
Structure Type MOL
InChI Key GXPHKUHSUJUWKP-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

CI-991 CS-045 GR-92132X GR92132X Prelay Rezulin Romozin Troglitazona Troglitazone
45
Targets
101
Activities
3
Assay Types
30
PK Parameters
20
Publications
9
Known Names
2
Indications
1
Mechanisms

Molecular Properties

441.6
MW (Da)
4.37
ALogP
6
HBA
2
HBD
84.9
PSA (Ų)
0.72
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1997
Availability Withdrawn
Chirality Racemic

Routes of Administration

Oral

Flags

Withdrawn Natural Product
USAN Stem -glitazone
USAN Year 1995

Extended Properties

Molecular Formula C24H27NO5S
MW 441.55
Aromatic Rings 2
Heavy Atoms 31
NP-Likeness 1.04

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Peroxisome proliferator-activated receptor gamma agonist AGONIST Peroxisome proliferator-activated receptor gamma

Indications

Diabetes Mellitus Sarcoma

ATC Classification

A10BG01
troglitazone
Level 1: ALIMENTARY TRACT AND METABOLISM
Level 2: DRUGS USED IN DIABETES

Drug Warnings

Withdrawn
hepatotoxicity
hepatic necrosis and failure, with a mean time to onset of 3 months.
Country: Peru; United Kingdom; United States   Year: 1997
Withdrawn
hepatotoxicity
hepatic necrosis and failure, with a mean time to onset of 3 months.
Country: Peru; United Kingdom; United States   Year: 1997
Withdrawn
hepatotoxicity
Hepatotoxicity
Country: Peru; United Kingdom; United States   Year: 1997
Withdrawn
hepatotoxicity
Severe hepatic adverse effects
Country: Peru; United Kingdom; United States   Year: 1997
Withdrawn
hepatotoxicity
hepatic necrosis and failure, with a mean time to onset of 3 months.
Country: Peru; United Kingdom; United States   Year: 1997
Withdrawn
hepatotoxicity
Severe hepatic adverse effects
Country: Peru; United Kingdom; United States   Year: 1997
Withdrawn
hepatotoxicity
Hepatotoxicity
Country: Peru; United Kingdom; United States   Year: 1997
Withdrawn
hepatotoxicity
hepatic necrosis and failure, with a mean time to onset of 3 months.
Country: Peru; United Kingdom; United States   Year: 1997

Activity Summary

IC50 58 meas. best 7.27
EC50 29 meas. best 7.0
Ki 14 meas. best 7.28

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Forkhead box protein M1
CHEMBL4739852
Ki 7.28 7.28 52.0 1
Liver
CHEMBL613642
IC50 7.27 7.27 53.2 1
Mesenchymal stem cells
CHEMBL5058627
EC50 7.0 7.0 100.0 1
3T3-L1
CHEMBL614510
EC50 6.89 6.89 130.0 2
Peroxisome proliferator-activated receptor gamma
CHEMBL235
Ki 6.7 6.33 200.0 6
Peroxisome proliferator-activated receptor gamma
CHEMBL235
EC50 6.67 6.0855 215.0 20
Peroxisome proliferator-activated receptor gamma
CHEMBL235
IC50 6.52 6.13 300.0 6
Peroxisome proliferator-activated receptor gamma
CHEMBL2459
EC50 6.11 6.055 780.0 2
Voltage-dependent L-type calcium channel subunit alpha-1C
CHEMBL2366456
IC50 6.1 6.1 800.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 6.08 6.08 835.0 1
Unchecked
CHEMBL612545
EC50 6.07 6.07 860.0 1
Carbonic anhydrase 2
CHEMBL205
IC50 6.01 6.01 970.0 1
Mitogen-activated protein kinase 1
CHEMBL4040
IC50 5.91 5.91 1238.0 1
Unchecked
CHEMBL612545
IC50 5.89 5.3314 1299.3 7
5-hydroxytryptamine receptor 2B
CHEMBL1833
IC50 5.88 5.88 1312.0 1
Aldo-keto reductase family 1 member B1
CHEMBL2622
IC50 5.69 5.69 2038.0 1
Amine oxidase [flavin-containing] B
CHEMBL2039
IC50 5.68 5.68 2070.0 2
Bile salt export pump
CHEMBL6020
IC50 5.57 5.16 2700.0 7
Thromboxane-A synthase
CHEMBL1835
IC50 5.53 5.53 2966.0 1
Adenosine receptor A3
CHEMBL256
Ki 5.53 5.53 2943.0 1
Bile salt export pump
CHEMBL2073674
IC50 5.41 5.19 3900.0 2
Cytochrome P450 2C9
CHEMBL3397
IC50 5.4 5.4 4000.0 1
Leishmania donovani
CHEMBL367
IC50 5.37 5.37 4260.0 1
Indoleamine 2,3-dioxygenase 2
CHEMBL2189159
IC50 5.35 5.35 4500.0 1
Amine oxidase [flavin-containing] A
CHEMBL3358
Ki 5.32 5.32 4800.0 1
Adenosine receptor A3
CHEMBL256
IC50 5.28 5.28 5208.0 1
Nuclear receptor subfamily 1 group I member 2
CHEMBL3401
EC50 5.16 4.9033 6900.0 3
Plasmodium falciparum
CHEMBL364
IC50 5.14 5.14 7270.0 1
Amine oxidase [flavin-containing] B
CHEMBL2039
Ki 5.02 5.02 9500.0 1
Voltage-dependent L-type calcium channel subunit alpha-1C
CHEMBL3762
IC50 5.02 5.02 9500.0 1
Hepatitis B virus
CHEMBL613497
IC50 5.0 5.0 10000.0 1
Amine oxidase [flavin-containing] A
CHEMBL1951
Ki 4.98 4.98 10500.0 1
Amine oxidase [flavin-containing] B
CHEMBL2993
Ki 4.96 4.96 10900.0 1
PC-12
CHEMBL612556
IC50 4.82 4.82 15000.0 1
MDA-MB-231
CHEMBL400
IC50 4.8 4.57 15700.0 2
Polyunsaturated fatty acid lipoxygenase ALOX15
CHEMBL3259476
IC50 4.7 4.7 20000.0 1
UDP-glucuronosyltransferase 1-6
CHEMBL1743316
Ki 4.7 4.7 20000.0 1
LNCaP
CHEMBL612518
IC50 4.66 4.66 22000.0 1
PC-3
CHEMBL390
IC50 4.52 4.52 30000.0 1
ATP-binding cassette sub-family C member 3
CHEMBL5918
IC50 4.51 4.51 31000.0 1
Trypanosoma cruzi
CHEMBL368
IC50 4.49 4.49 32610.0 1
MCF7
CHEMBL387
IC50 4.45 4.29 35400.0 2
HT-29
CHEMBL384
IC50 4.3 4.3 50000.0 1
HCT-15
CHEMBL612263
IC50 4.29 4.29 50900.0 1
Tyrosine-protein phosphatase non-receptor type 1
CHEMBL335
IC50 4.26 4.26 55000.0 1
Trypanosoma brucei rhodesiense
CHEMBL612348
IC50 4.23 4.23 59340.0 1
ATP-binding cassette sub-family C member 4
CHEMBL1743128
IC50 4.21 4.21 61000.0 1
Indoleamine 2,3-dioxygenase 1
CHEMBL1075294
IC50 4.21 4.21 61000.0 1
LoVo
CHEMBL614721
IC50 4.19 4.19 65000.0 1
MDA-MB-453
CHEMBL614334
IC50 4.17 4.17 67100.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 25940.0 ng.hr.mL-1 Rattus norvegicus
AUC 27400.0 ng.hr.mL-1 Rattus norvegicus
AUC 5090.0 ng.hr.mL-1 Rattus norvegicus
AUC 5680.0 ng.hr.mL-1 Rattus norvegicus
AUC 25.94 u-1 hr-1 ml-1 Rattus norvegicus
AUC 27.4 u-1 hr-1 ml-1 Rattus norvegicus
AUC 25940.0 ng.hr.mL-1 Rattus norvegicus
AUC 27400.0 ng.hr.mL-1 Rattus norvegicus
AUC 9952.54 ng.hr.mL-1 Homo sapiens
CL 9.0 mL.min-1.kg-1 Homo sapiens
CL 3.5 mL.min-1.kg-1 Homo sapiens
CL 6.6 mL.min-1.kg-1 Canis lupus familiaris
CL 8.3 mL.min-1.kg-1 Macaca
CL 22.0 mL.min-1.kg-1 Rattus norvegicus
CL 28.18 uL.min-1.(10^6cells)-1 Homo sapiens
CL 48.98 mL.min-1.g-1 Homo sapiens
CL 150.0 uL.min-1.(10^6cells)-1 Rattus norvegicus
Cmax 12388.18 nM Rattus norvegicus
Cmax 0.77 μg/mL Rattus norvegicus
Cmax 12388.18 nM Rattus norvegicus
Cmax 12388.18 nM Rattus norvegicus
Cmax 6300.0 nM Homo sapiens
Cmax 6387.0 nM Homo sapiens
T1/2 4.01 hr Rattus norvegicus
T1/2 3.9 hr Rattus norvegicus
T1/2 4.01 hr Rattus norvegicus
T1/2 4.01 hr Rattus norvegicus
Tmax 2.25 hr Rattus norvegicus
Tmax 2.0 hr Rattus norvegicus
Tmax 2.25 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Forkhead box protein M1 Ki = 51.97 nM 7.28 Binding affinity to recombinant FOXM1 DBD (unknown origin) expressed in Escheric... 33069434
Liver IC50 = 53.2 nM 7.27 Induction of mitochondrial dysfunction in Sprague-Dawley rat liver mitochondria ... 24799086
Mesenchymal stem cells EC50 = 100.0 nM 7.0 Induction of adiponectin synthesis in human differentiated BMMSC cells measured ... 34922307
3T3-L1 EC50 = 130.0 nM 6.89 Effective concentration for 50% enhancement of insulin-induced triglyceride accu... 9599241
3T3-L1 EC50 = 130.0 nM 6.89 Effective concentration for 50% enhancement of insulin-induced triglyceride accu... 9599241
Peroxisome proliferator-activated receptor gamma Ki = 200.0 nM 6.7 Binding affinity to PPARgamma (unknown origin) assessed as inhibition constant b... 34922307
Peroxisome proliferator-activated receptor gamma EC50 = 215.0 nM 6.67 Agonist activity at PPARgamma (unknown origin) incubated for 3 to 16 hrs by path... 31312410
Peroxisome proliferator-activated receptor gamma Ki = 302.0 nM 6.52 In vitro binding to peroxisome proliferator activated receptor gamma (PPAR gamma... 9836620
Peroxisome proliferator-activated receptor gamma Ki = 302.0 nM 6.52 Binding affinity against Peroxisome proliferator activated receptor gamma (PPAR ... 10612594
Peroxisome proliferator-activated receptor gamma IC50 = 300.0 nM 6.52 Binding affinity to GST-tagged human PPARgamma by TR-FRET analysis 22579420
Peroxisome proliferator-activated receptor gamma EC50 = 340.0 nM 6.47 Agonist activity at human PPARgamma 37336069
Peroxisome proliferator-activated receptor gamma IC50 = 340.0 nM 6.47 Agonist activity at PPARgamma (unknown origin) 26048793
Peroxisome proliferator-activated receptor gamma IC50 = 370.0 nM 6.43 Competitive displacement of fluorescently labelled PPAR tracer ligand from GST-t... 30429097
Peroxisome proliferator-activated receptor gamma Ki = 380.0 nM 6.42 Displacement of fluormone Pan-PPAR Green from human GST-tagged PPARgamma-LBD by ... 29398443
Peroxisome proliferator-activated receptor gamma Ki = 400.0 nM 6.4 Binding affinity to human recombinant PPARgamma by Cheng-Prusoff equation based ... 30352713
Peroxisome proliferator-activated receptor gamma EC50 = 400.0 nM 6.4 Activation of PPARgamma transfected in HEK293 cells after 18 hrs by firefly luci... 21800856
Peroxisome proliferator-activated receptor gamma EC50 = 400.0 nM 6.4 Transactivation of human PPARgamma expressed in african green monkey CV1 cells b... 22579420
Peroxisome proliferator-activated receptor gamma EC50 = 440.0 nM 6.36 Agonist activity at human recombinant PPARgamma expressed in CHO cells cotransfe... 22424300
Peroxisome proliferator-activated receptor gamma EC50 = 440.0 nM 6.36 Agonist activity at human PPARgamma expressed in CHO cells co-transfected with p... 22342624
Peroxisome proliferator-activated receptor gamma EC50 = 537.03 nM 6.27 Transcriptional activation of peroxisome proliferator activated receptor gamma 10612594

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885881 Rattus norvegicus 128
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
21493073 10.1016/j.bmc.2011.03.040 3T3-L1 14
10354401 10.1021/jm980549x Rattus norvegicus 12
10464013 10.1021/jm9805541 Rattus norvegicus 12
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
23910984 10.1016/j.bmcl.2013.06.101 3T3-L1 11
17609121 10.1016/j.bmcl.2007.06.027 3T3-L1 10
30352713 10.1016/j.bmc.2018.10.010 PPAR alpha/gamma 10
31838327 10.1016/j.ejmech.2019.111939 MDA-MB-231 9
17609121 10.1016/j.bmcl.2007.06.027 Mus musculus 8
15920768 10.1002/jps.20373 ADMET 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
2913302 10.1021/jm00122a022 Mus musculus 8
20966043 10.1124/dmd.110.035105 Nuclear receptor subfamily 1 group I member 2 7
10354401 10.1021/jm980549x Mus musculus 6
30352713 10.1016/j.bmc.2018.10.010 Unchecked 6
7966158 10.1021/jm00049a017 Mus musculus 5
27777006 10.1016/j.bmcl.2016.10.033 NON-PROTEIN TARGET 5
- 10.1016/S0960-894X(97)00118-2 Mus musculus 5

Data from ChEMBL 36 via Core Engine