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Compound Detail

CHEMBL121

ROSIGLITAZONE
💊 Approved Drug
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💊 Approved Drug
CN(CCOc1ccc(CC2SC(=O)NC2=O)cc1)c1ccccn1

Basic Information

ChEMBL ID CHEMBL121
Name ROSIGLITAZONE
Phase Approved
Structure Type MOL
InChI Key YASAKCUCGLMORW-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Avandamet Avandaryl Avandia BRL-49653 Gaudil NSC-758698 Nyracta Rezult Rosiglitazona Rosiglitazone Rosiglizole Rosvel +2 more
34
Targets
316
Activities
4
Assay Types
30
PK Parameters
20
Publications
14
Known Names
20
Indications
1
Mechanisms

Molecular Properties

357.4
MW (Da)
2.49
ALogP
6
HBA
1
HBD
71.5
PSA (Ų)
0.82
QED
0
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1999
Availability Withdrawn
Chirality Racemic

Routes of Administration

Oral

Flags

Black Box Warning Withdrawn Natural Product
USAN Stem -glitazone
USAN Year 1997

Extended Properties

Molecular Formula C18H19N3O3S
MW 357.44
Aromatic Rings 2
Heavy Atoms 25
NP-Likeness -0.93

Mechanism of Action

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

Indications

Diabetes Mellitus Diabetes Mellitus, Type 2 Alzheimer Disease Atherosclerosis Cardiovascular Diseases Coronary Disease Diabetic Neuropathies Glucose Intolerance Glucose Intolerance Hypercholesterolemia Hypertension Lipid Metabolism Disorders Metabolic Diseases Metabolic Syndrome Multiple Organ Failure Prostatic Neoplasms Arthritis, Rheumatoid Asthma Cognitive Dysfunction Colitis, Ulcerative

ATC Classification

A10BG02
rosiglitazone
Level 1: ALIMENTARY TRACT AND METABOLISM
Level 2: DRUGS USED IN DIABETES

Drug Warnings

Withdrawn
cardiotoxicity
Increased cardiovascular risk outweighs its benefit; Cardiovascular risk; Elevated risk of cardiovascular events
Country: Armenia; Guatemala; Egypt; New Zealand; Madagascar; European Union   Year: 2010
Withdrawn
cardiotoxicity
Elevated risk of cardiovascular events
Country: Armenia; Guatemala; Egypt; New Zealand; Madagascar; European Union   Year: 2010

Activity Summary

EC50 198 meas. best 9.0
IC50 84 meas. best 8.11
Ki 25 meas. best 9.64
Kd 9 meas. best 8.92

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Type-1 angiotensin II receptor A
CHEMBL329
Ki 9.64 9.64 0.2 1
Peroxisome proliferator-activated receptor gamma
CHEMBL235
EC50 9.0 7.0904 1.0 159
Peroxisome proliferator-activated receptor gamma
CHEMBL235
Kd 8.92 6.9238 1.2 8
Unchecked
CHEMBL612545
EC50 8.7 7.1717 2.0 6
Peroxisome proliferator-activated receptor alpha
CHEMBL239
EC50 8.4 5.8489 4.0 18
Peroxisome proliferator-activated receptor gamma
CHEMBL235
Ki 8.24 7.3858 5.8 19
Peroxisome proliferator-activated receptor gamma
CHEMBL235
IC50 8.11 6.8938 7.7 47
U2OS
CHEMBL615023
EC50 7.52 7.52 30.0 1
Peroxisome proliferator-activated receptor gamma
CHEMBL2459
EC50 7.52 7.2867 30.0 3
CDGSH iron-sulfur domain-containing protein 1
CHEMBL1795168
Ki 7.51 7.51 31.0 1
Peroxisome proliferator-activated receptor alpha
CHEMBL2128
IC50 7.1 7.1 80.0 1
3T3-L1
CHEMBL614510
EC50 6.92 6.34 120.0 2
Unchecked
CHEMBL612545
IC50 6.9 5.9633 125.0 3
Unchecked
CHEMBL612545
Kd 6.43 6.43 370.0 1
CDGSH iron-sulfur domain-containing protein 1
CHEMBL1795168
IC50 6.14 6.14 731.0 1
Amine oxidase [flavin-containing] B
CHEMBL2039
IC50 6.08 6.08 832.0 2
HUVEC
CHEMBL613979
IC50 5.96 5.96 1100.0 1
CDGSH iron-sulfur domain-containing protein 1
CHEMBL3308979
IC50 5.96 5.96 1100.0 1
Peroxisome proliferator-activated receptor
CHEMBL3559683
EC50 5.8 5.8 1600.0 1
CDGSH iron-sulfur domain-containing protein 2
CHEMBL4523399
IC50 5.64 5.64 2290.0 1
Bile salt export pump
CHEMBL6020
IC50 5.55 5.3583 2800.0 6
Thromboxane-A synthase
CHEMBL1835
IC50 5.45 5.45 3560.0 1
Peroxisome proliferator-activated receptor delta
CHEMBL3979
EC50 5.44 5.2567 3620.0 3
Carbonic anhydrase 2
CHEMBL205
IC50 5.39 5.39 4069.0 1
Amine oxidase [flavin-containing] B
CHEMBL2039
Ki 5.38 5.38 4200.0 1
L6
CHEMBL614793
EC50 5.35 5.325 4490.0 2
L6
CHEMBL614793
IC50 5.32 5.32 4800.0 1
Hepatic sodium/bile acid cotransporter
CHEMBL5287
IC50 5.29 5.29 5100.0 1
Hepatitis B virus
CHEMBL613497
IC50 5.29 5.29 5100.0 1
MDA-MB-231
CHEMBL400
IC50 5.28 5.28 5230.0 1
Amine oxidase [flavin-containing] B
CHEMBL2993
Ki 5.24 5.24 5800.0 1
Keratinocyte
CHEMBL613995
IC50 5.1 5.1 8000.0 1
Free fatty acid receptor 1
CHEMBL4422
EC50 4.94 4.94 11481.5 1
DU-145
CHEMBL613508
IC50 4.8 4.8 16000.0 1
RAW264.7
CHEMBL612557
IC50 4.76 4.76 17500.0 1
PC-3
CHEMBL390
IC50 4.69 4.69 20300.0 1
ATP-binding cassette sub-family C member 4
CHEMBL1743128
IC50 4.68 4.68 21000.0 1
Amine oxidase [flavin-containing] A
CHEMBL1951
Ki 4.56 4.56 27600.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 4.53 4.53 29500.0 1
Amine oxidase [flavin-containing] A
CHEMBL3358
Ki 4.49 4.49 32600.0 1
Bile salt export pump
CHEMBL2073674
IC50 4.4 4.4 40000.0 1
HT-29
CHEMBL384
IC50 4.35 4.35 45000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 5862.02 ng.hr.mL-1 Rattus norvegicus
AUC 5862.02 ng.hr.mL-1 Rattus norvegicus
AUC 873922.0 ng min -
AUC 14565.37 ng.hr.mL-1 Rattus norvegicus
AUC 4080.0 ng.hr.mL-1 Rattus norvegicus
AUC 113308.48 ng.hr.mL-1 Mus musculus
AUC 574406.08 ng.hr.mL-1 Rattus norvegicus
AUC 250208.0 ng.hr.mL-1 Mus musculus
AUC 965088.0 ng.hr.mL-1 Rattus norvegicus
AUC 19194.53 ng.hr.mL-1 Rattus norvegicus
AUC 33670.85 ng.hr.mL-1 Rattus norvegicus
AUC 207672.64 ng.hr.mL-1 Rattus norvegicus
AUC 114380.8 ng.hr.mL-1 Mus musculus
AUC 3216.96 ng.hr.mL-1 Rattus norvegicus
AUC 21839.58 ng.hr.mL-1 Rattus norvegicus
AUC 208637.73 ng.hr.mL-1 Rattus norvegicus
AUC 2308347.52 ng.hr.mL-1 Rattus norvegicus
AUC 5862.02 ng.hr.mL-1 Rattus norvegicus
AUC 113308.48 ng.hr.mL-1 Mus musculus
AUC 214464.0 ng.hr.mL-1 Rattus norvegicus
AUC 78636.8 ng.hr.mL-1 Mus musculus
AUC 2865.6 ng.hr.mL-1 Homo sapiens
AUC 7.068 ng.hr.mL-1 Rattus norvegicus
AUC - - Rattus norvegicus
AUC 6550.0 ng.hr.mL-1 Rattus norvegicus
AUC 525000.0 ng.hr.mL-1 Rattus norvegicus
AUC - - Rattus norvegicus
CL 2.7 mL.min-1.kg-1 Rattus norvegicus
CL 2.7 mL.min-1.kg-1 Rattus norvegicus
CL 2.1 mL.min-1.kg-1 -

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Type-1 angiotensin II receptor A Ki = 0.23 nM 9.64 Displacement of [125I]-SI-Ang-2 from AT1 receptor in Rattus norvegicus Sprague-D... -
Peroxisome proliferator-activated receptor gamma EC50 = 1.0 nM 9.0 Kinase Activity Assay: After 24 h treatment with the medicament, the cells were ... -
Peroxisome proliferator-activated receptor gamma Kd = 1.2 nM 8.92 Binding affinity to PPARgamma (unknown origin) assessed as thermodynamic dissoci... 28076827
Unchecked EC50 = 2.0 nM 8.7 Agonist activity at GAL4-fused PPARgamma M463A mutant (unknown origin) expressed... 23502212
Peroxisome proliferator-activated receptor gamma EC50 = 2.4 nM 8.62 Agonist activity at PPARgamma LBD in human 293H DA cells after 16 hrs by TR-FRET... 22582973
Peroxisome proliferator-activated receptor gamma EC50 = 2.7 nM 8.57 Activation of wild type PPAR-gamma-mediated transcriptional activity assessed as... 17403688
Peroxisome proliferator-activated receptor gamma EC50 = 3.8 nM 8.42 Activation of human PPARgamma ligand binding domain-mediated transcriptional act... 17403688
Peroxisome proliferator-activated receptor gamma EC50 = 4.0 nM 8.4 In vitro effective concentration against human peroxisome proliferator activated... 16137885
Peroxisome proliferator-activated receptor gamma EC50 = 4.0 nM 8.4 Agonist activity at human PPARgamma expressed in African green monkey COS7 cells... 31268307
Peroxisome proliferator-activated receptor gamma EC50 = 4.0 nM 8.4 Transactivation of human Gal4-fused PPARgamma LBD expressed in African green mon... 28609708
Peroxisome proliferator-activated receptor gamma EC50 = 4.0 nM 8.4 Agonist at human PPARgamma LBD expressed in human HEK293 cells cotransfected wit... 23286787
Peroxisome proliferator-activated receptor alpha EC50 = 4.0 nM 8.4 Agonist activity at human PPARalpha at 100 uM by GAL4 transactivation assay rela... 18255290
Peroxisome proliferator-activated receptor gamma Ki = 5.8 nM 8.24 Binding affinity to human PPARgamma receptor by radioligand displacement assay 23466604
Peroxisome proliferator-activated receptor gamma Kd = 7.0 nM 8.15 Binding affinity to human PPARgamma (unknown origin) by competitive TR-FRET assa... 23286787
Peroxisome proliferator-activated receptor gamma IC50 = 7.7 nM 8.11 Agonist activity at PPARg-LBD (unknown origin) expressed in HEK293 cells assesse... 33142057
Peroxisome proliferator-activated receptor gamma EC50 = 8.0 nM 8.1 Transactivation of GAL4-DBD fused human PPARgamma ligand binding domain expresse... 30429097
Peroxisome proliferator-activated receptor gamma Ki = 8.0 nM 8.1 Displacement of [3H]Rosiglitazone from human PPARgamma 18255290
Peroxisome proliferator-activated receptor gamma Ki = 8.0 nM 8.1 Binding affinity for human PPAR gamma construct expressed in bacteria with 3[H] ... 16137885
Peroxisome proliferator-activated receptor gamma EC50 = 9.0 nM 8.05 Agonist activity at human PPARgamma transfected in HEK293 cells assessed increas... 28231521
Peroxisome proliferator-activated receptor gamma IC50 = 10.0 nM 8.0 Displacement of [3H]rosiglitazone from human recombinant PPARgamma receptor expr... 26988801

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885881 Rattus norvegicus 467
- 10.5281/zenodo.13943903 ADMET 89
31158845 10.1038/s41586-019-1291-3 ADMET 59
28735214 10.1016/j.ejmech.2017.07.015 Rattus norvegicus 37
33142057 10.1021/acs.jmedchem.0c01555 Unchecked 26
11831892 10.1021/jm010964g Mus musculus 23
30220602 10.1016/j.bmc.2018.09.005 Rattus norvegicus 22
19507861 10.1021/jm900097m Rattus norvegicus 20
19530681 10.1021/jm900367w Rattus norvegicus 18
29446942 10.1021/acs.jmedchem.7b01285 Peroxisome proliferator-activated receptor gamma 16
27839787 10.1016/j.ejmech.2016.11.015 Mus musculus 16
30241907 10.1016/j.bmc.2018.09.006 Rattus norvegicus 15
32603982 10.1016/j.ejmech.2020.112315 Mus musculus 15
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
33142057 10.1021/acs.jmedchem.0c01555 Peroxisome proliferator-activated receptor gamma 13
30481687 10.1016/j.ejmech.2018.10.006 Platelet 12
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
22197396 10.1016/j.bmc.2011.11.035 Mus musculus 11
22727448 10.1016/j.ejmech.2012.05.040 Rattus norvegicus 11
12657263 10.1016/s0960-894x(03)00115-x Rattus norvegicus 10

Data from ChEMBL 36 via Core Engine