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Compound Detail

CHEMBL957

BOSENTAN
💊 Approved Drug
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💊 Approved Drug
COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(-c2ncccn2)nc1OCCO

Basic Information

ChEMBL ID CHEMBL957
Name BOSENTAN
Phase Approved
Structure Type MOL
InChI Key GJPICJJJRGTNOD-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Anhydrous bosentan Bosentan Bosentan (as monohydrate) Bosentan anhydrous Bosentan hydrate Bosentan monohydrate RO 47-0203/029 RO-47-0203-029 RO-47-0203/029 RO-470203029 Stayveer Tracleer
14
Targets
54
Activities
4
Assay Types
22
PK Parameters
20
Publications
12
Known Names
20
Indications
1
Mechanisms

Molecular Properties

551.6
MW (Da)
4.20
ALogP
10
HBA
2
HBD
145.7
PSA (Ų)
0.29
QED
1
Ro5 Violations
10
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2001
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Black Box Warning Natural Product
USAN Stem -entan
USAN Year 1995

Extended Properties

Molecular Formula C27H29N5O6S
MW 551.63
Aromatic Rings 4
Heavy Atoms 39
NP-Likeness -1.01

Mechanism of Action

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

Indications

Familial Primary Pulmonary Hypertension Heart Defects, Congenital Hypertension Hypertension, Pulmonary Hypertension, Pulmonary Pulmonary Arterial Hypertension Scleroderma, Systemic Diabetes Mellitus, Type 2 Eisenmenger Complex Heart Septal Defects, Atrial Idiopathic Pulmonary Fibrosis Optic Neuropathy, Ischemic Persistent Fetal Circulation Syndrome Ulcer Asthma Hermanski-Pudlak Syndrome Hernias, Diaphragmatic, Congenital Hypoplastic Left Heart Syndrome Liver Cirrhosis Melanoma

ATC Classification

C02KX01
bosentan
Level 1: CARDIOVASCULAR SYSTEM
Level 2: ANTIHYPERTENSIVES

Drug Warnings

Black Box Warning
teratogenicity
Country: United States
Black Box Warning
hepatotoxicity
Country: United States

Activity Summary

IC50 36 meas. best 8.33
Ki 10 meas. best 8.44
EC50 4 meas. best 6.28
Kd 4 meas. best 7.4

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Endothelin-1 receptor
CHEMBL252
Ki 8.44 8.23 3.7 4
Endothelin-1 receptor
CHEMBL252
IC50 8.33 7.4954 4.7 13
Endothelin-1 receptor
CHEMBL4566
IC50 8.33 8.33 4.7 1
Endothelin-1 receptor
CHEMBL4566
Ki 8.19 8.19 6.5 1
Endothelin-1 receptor
CHEMBL4130
IC50 8.12 8.12 7.5 1
Endothelin-1 receptor
CHEMBL4566
Kd 7.4 7.28 39.8 3
Endothelin receptor type B
CHEMBL1785
Ki 7.1 6.6 80.0 4
Endothelin receptor type B
CHEMBL1785
IC50 7.02 6.6638 95.0 8
Endothelin receptor type B
CHEMBL4631
IC50 7.02 7.02 95.0 1
Unchecked
CHEMBL612545
EC50 6.28 6.28 530.0 1
Endothelin receptor type B
CHEMBL4631
Kd 5.8 5.8 1584.9 1
Nuclear receptor subfamily 1 group I member 2
CHEMBL3401
EC50 5.05 4.9333 8900.0 3
Bile salt export pump
CHEMBL2073674
Ki 4.92 4.92 12000.0 1
ATP-binding cassette sub-family C member 4
CHEMBL1743128
IC50 4.66 4.66 22000.0 1
Bile salt export pump
CHEMBL6020
IC50 4.66 4.565 22000.0 4
Bile salt export pump
CHEMBL2073674
IC50 4.51 4.51 30600.0 1
ATP-binding cassette sub-family C member 3
CHEMBL5918
IC50 4.38 4.38 42000.0 1
SK-MEL-28
CHEMBL614919
IC50 4.27 4.27 53650.0 1
Deoxyhypusine synthase
CHEMBL4415
IC50 4.22 4.22 60830.0 1
A-375
CHEMBL613859
IC50 4.17 4.17 67360.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 8914.34 ng.hr.mL-1 Homo sapiens
CL 55.0 mL.min-1.kg-1 Rattus norvegicus
CL 1.9 mL.min-1.kg-1 Canis lupus familiaris
CL 3.7 mL.min-1.kg-1 Homo sapiens
CL 2.1 mL.min-1.kg-1 Homo sapiens
CL 4.79 uL.min-1.(10^6cells)-1 Homo sapiens
CL 15.14 mL.min-1.g-1 Homo sapiens
CL 16.0 mL.min-1.kg-1 Homo sapiens
CL 15.9 mL.min-1.kg-1 Rattus norvegicus
CL 33.1 mL.min-1.kg-1 Macaca fascicularis
CL 2.2 mL.min-1.kg-1 Homo sapiens
Cmax 7433.0 nM Homo sapiens
F 30.0 % Rattus norvegicus
F 50.0 % Homo sapiens
Fu 0.037 - Homo sapiens
Fu 0.000121 - Rattus norvegicus
Fu 0.000422 - Macaca fascicularis
Fu 0.000285 - Homo sapiens
MRT 2.3 hr Homo sapiens
T1/2 4.0 hr Rattus norvegicus
T1/2 4.1 hr Homo sapiens
T1/2 0.01667 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Endothelin-1 receptor Ki = 3.67 nM 8.44 Displacement of [125I]endhothelin-1 from human ETA receptor stably expressed in ... 10082200
Endothelin-1 receptor IC50 = 4.7 nM 8.33 Displacement of [125I]ET-1 from rat ETA receptor after 1 hr by Lowry method 25614116
Endothelin-1 receptor IC50 = 4.7 nM 8.33 Binding affinity to human ETA receptor 27318985
Endothelin-1 receptor IC50 = 4.7 nM 8.33 Antagonist activity against human ET-1 by ELISA analysis 37515921
Endothelin-1 receptor Ki = 6.5 nM 8.19 Binding affinity to ETA receptor (unknown origin) assessed as inhibition constan... 10082200
Endothelin-1 receptor Ki = 6.5 nM 8.19 Binding affinity towards Endothelin A receptor 15055997
Endothelin-1 receptor Ki = 6.5 nM 8.19 Ability to displace endothelin ([125I]ET1) from human Endothelin A receptor 9379441
Endothelin-1 receptor IC50 = 7.5 nM 8.12 In vitro inhibition of [125 I]ET-1 binding to Endothelin A receptor in porcine a... 11738578
Endothelin-1 receptor Ki = 8.0 nM 8.1 Inhibitory activity against human endothelin A receptor expressed in CHO cells 12502366
Endothelin-1 receptor IC50 = 8.0 nM 8.1 Receptor binding affinity was determined in a radioligand binding assay against ... -
Endothelin-1 receptor IC50 = 8.4 nM 8.08 Displacement of 125I-labelled endothelin-1 from human ETA receptor expressed in ... -
Endothelin-1 receptor IC50 = 8.9 nM 8.05 Antagonist activity at human endothelin receptor subtype A expressed in CHO-K1 c... 22750010
Endothelin-1 receptor Kd = 39.81 nM 7.4 Antagonist activity at rat aortic ring ETA receptor in presence of ET1 27321813
Endothelin-1 receptor IC50 = 40.0 nM 7.4 In vitro inhibitory concentration required against [125I]ET1 binding to membrane... 12617929
Endothelin-1 receptor IC50 = 45.0 nM 7.35 Displacement of [I125]ET1 from recombinant ETA receptor expressed in CHO cells a... 22862294
Endothelin-1 receptor IC50 = 45.0 nM 7.35 Displacement of 125I-ET1 from human smooth muscle ETA receptor 27321813
Endothelin-1 receptor IC50 = 45.0 nM 7.35 Antagonist activity at ET-A receptor (unknown origin) 27266371
Endothelin-1 receptor Kd = 50.12 nM 7.3 Compound was evaluated for in vitro functional inhibitory potency for prevention... -
Endothelin-1 receptor Kd = 72.44 nM 7.14 Potency on ETA receptor assessed by inhibition of the contraction induced by ET-... 12617929
Endothelin-1 receptor IC50 = 80.0 nM 7.1 Receptor binding affinity was determined against [125I]ET1 with recombinant huma... -

Literature References

PubMed DOI Target Context # Activities
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
32985885 10.1021/acs.jmedchem.0c01033 ADMET 11
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
20966043 10.1124/dmd.110.035105 Nuclear receptor subfamily 1 group I member 2 7
22862294 10.1021/jm3009103 Rattus norvegicus 5
27318985 10.1016/j.ejmech.2016.06.006 Cytochrome P450 3A4 4
18426954 10.1124/dmd.108.020479 ADMET 4
- 10.6019/CHEMBL3301361 ADMET 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
37468498 10.1038/s41467-023-40064-9 Bile acid receptor 4
- 10.1016/S0960-894X(97)00400-9 Endothelin-1 receptor 4
27318985 10.1016/j.ejmech.2016.06.006 ADMET 4
37468498 10.1038/s41467-023-40064-9 Histamine H1 receptor 3
37468498 10.1038/s41467-023-40064-9 Glucocorticoid receptor 3
20014752 10.1021/tx900326k Hepatotoxicity 3
- 10.1016/S0960-894X(97)00400-9 Endothelin receptor type B 3
31021628 10.1021/acs.jmedchem.9b00123 Rattus norvegicus 3
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 3
23956101 10.1093/toxsci/kft176 Unchecked 3

Data from ChEMBL 36 via Core Engine