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Compound Detail

CHEMBL282724

SITAXENTAN
💊 Approved Drug
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💊 Approved Drug
Cc1cc2c(cc1CC(=O)c1sccc1S(=O)(=O)Nc1onc(C)c1Cl)OCO2
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL282724
Name SITAXENTAN
Phase Approved
Structure Type MOL
InChI Key PHWXUGHIIBDVKD-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

IPI-1040 Sitaxentan Sitaxsentan TBC-11251
8
Targets
14
Activities
3
Assay Types
15
PK Parameters
20
Publications
4
Known Names
6
Indications
1
Mechanisms

Molecular Properties

454.9
MW (Da)
3.96
ALogP
8
HBA
1
HBD
107.7
PSA (Ų)
0.56
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2006
Availability Withdrawn
Chirality Achiral

Routes of Administration

Oral

Flags

Withdrawn Natural Product
USAN Stem -entan
USAN Year 2011

Extended Properties

Molecular Formula C18H15ClN2O6S2
MW 454.91
Aromatic Rings 3
Heavy Atoms 29
NP-Likeness -1.45

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Endothelin receptor, ET-A/ET-B antagonist ANTAGONIST Endothelin receptor, ET-A/ET-B ✓ ✓

Indications

Hypertension Hypertension, Pulmonary Hypertension, Pulmonary Asthma Proteinuria Renal Insufficiency, Chronic

ATC Classification

C02KX03
sitaxentan
Level 1: CARDIOVASCULAR SYSTEM
Level 2: ANTIHYPERTENSIVES

Drug Warnings

Withdrawn
hepatotoxicity
Hepatotoxicity
Country: Worldwide   Year: 2010
Withdrawn
hepatotoxicity
Hepatotoxicity
Country: Worldwide   Year: 2010
Withdrawn
hepatotoxicity
Risk of acute liver failure
Country: Worldwide   Year: 2010
Withdrawn
hepatotoxicity
Risk of acute liver failure
Country: Worldwide   Year: 2010

Activity Summary

IC50 9 meas. best 8.85
Ki 4 meas. best 9.37
Kd 1 meas. best 8.0

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Endothelin-1 receptor
CHEMBL252
 Ki 9.37 9.37 0.4 2
Endothelin-1 receptor
CHEMBL4566
 Ki 9.37 9.37 0.4 1
Rattus norvegicus
CHEMBL376
 Ki 9.16 9.16 0.7 1
Endothelin-1 receptor
CHEMBL252
 IC50 8.85 8.85 1.4 4
Unchecked
CHEMBL612545
 Kd 8.0 8.0 10.0 1
Endothelin receptor type B
CHEMBL1785
 IC50 5.01 5.01 9800.0 1
Bile salt export pump
CHEMBL6020
 IC50 4.9 4.9 12600.0 1
ATP-binding cassette sub-family C member 4
CHEMBL1743128
 IC50 4.55 4.55 28400.0 1
ATP-binding cassette sub-family C member 3
CHEMBL5918
 IC50 4.34 4.34 45400.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 33020.0 ng.hr.mL-1 Homo sapiens
AUC 21799.29 ng.hr.mL-1 Homo sapiens
Cmax 36117.03 nM Rattus norvegicus
Cmax 269943.51 nM Rattus norvegicus
F 60.0 % Rattus norvegicus
F 60.0 % Rattus norvegicus
F 90.0 % Canis lupus familiaris
F 60.0 % Rattus norvegicus
F 60.0 % Canis lupus familiaris
T1/2 6.46 hr Rattus norvegicus
T1/2 7.5 hr Rattus norvegicus
T1/2 4.8 hr Canis lupus familiaris
T1/2 6.46 hr Homo sapiens
T1/2 4.1 hr Rattus norvegicus
T1/2 6.7 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Endothelin-1 receptor Ki = 0.43 nM 9.37 Binding affinity towards Endothelin A receptor 15055997
Endothelin-1 receptor Ki = 0.43 nM 9.37 Binding affinity against human Endothelin A receptor 9171878
Endothelin-1 receptor Ki = 0.43 nM 9.37 Displacement of [125I]ET-1 from ETA receptor in human TE-671 cells Membrane asse... 10082200
Rattus norvegicus Ki = 0.686 nM 9.16 Inhibition of ET1 induced stimulation of phosphoinositide turnover 9171878
Endothelin-1 receptor IC50 = 1.4 nM 8.85 Inhibitory concentration towards Endothelin A receptor in human 15055997
Endothelin-1 receptor IC50 = 1.4 nM 8.85 Displacement of [125I]ET-1 from Endothelin A receptor 15055997
Endothelin-1 receptor IC50 = 1.4 nM 8.85 Inhibitory concentration was determined against selective Endothelin A receptor 11312921
Endothelin-1 receptor IC50 = 1.4 nM 8.85 In vitro inhibition of endothelin binding to human Endothelin A receptor using [... 9171878
Unchecked Kd = 10.0 nM 8.0 Phosphoinositol hydrolysis in TE671 or transfected cos 7 cells 9171878
Endothelin receptor type B IC50 = 9800.0 nM 5.01 In vitro inhibition of endothelin binding to human Endothelin B receptor using [... 9171878
Bile salt export pump IC50 = 12600.0 nM 4.9 Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as... 23956101
ATP-binding cassette sub-family C member 4 IC50 = 28400.0 nM 4.55 Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as... 23956101
ATP-binding cassette sub-family C member 3 IC50 = 45400.0 nM 4.34 Inhibition of human MRP3 overexpressed in Sf9 insect cell membrane vesicles asse... 23956101

Literature References

PubMed DOI Target Context # Activities
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
15055997 10.1021/jm030528p Rattus norvegicus 6
9171878 10.1021/jm9700068 Rattus norvegicus 5
15055997 10.1021/jm030528p Endothelin-1 receptor 4
15055997 10.1021/jm030528p ADMET 3
20014752 10.1021/tx900326k Hepatotoxicity 3
23956101 10.1093/toxsci/kft176 Unchecked 3
37468498 10.1038/s41467-023-40064-9 D(1A) dopamine receptor 2
9171878 10.1021/jm9700068 ADMET 2
23956101 10.1093/toxsci/kft176 ATP-binding cassette sub-family C member 2 2
23956101 10.1093/toxsci/kft176 Homo sapiens 2
9171878 10.1021/jm9700068 Endothelin-1 receptor 2
27321813 10.1016/j.bmcl.2016.06.014 ADMET 2
10579813 10.1021/jm9900063 Rattus norvegicus 2
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
26948801 10.1016/j.drudis.2016.02.015 Homo sapiens 2
15055997 10.1021/jm030528p Canis familiaris 2
37468498 10.1038/s41467-023-40064-9 Thromboxane A2 receptor 2

Data from ChEMBL 36 via Core Engine