Bosentan

Summary

Bosentan (CHEMBL957) is an approved small-molecule antihypertensive agent (ATC C02KX01) targeting EDNRA and EDNRB; indicated across 27 conditions including pulmonary arterial hypertension and systemic sclerosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C02KX01
• Targets: 2 (EDNRA, EDNRB)
• Indications: 27 conditions
• Clinical trials: 95
• Chemistry: 551.6 Da · C27H29N5O6S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL957
Name	Bosentan
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	104865
ChEBI	CHEBI:51450
ATC	C02KX01
Molecular formula	C27H29N5O6S
Molecular weight	551.6
InChIKey	GJPICJJJRGTNOD-UHFFFAOYSA-N

SMILES: CC(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC2=C(C(=NC(=N2)C3=NC=CC=N3)OCCO)OC4=CC=CC=C4OC

IUPAC name: 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide

Pharmacological roles (ChEBI): antihypertensive agent, endothelin receptor antagonist.

Also known as: Anhydrous bosentan, Bosentan, Bosentan (as monohydrate), Bosentan anhydrous, Bosentan hydrate, Bosentan monohydrate, RO-470203029, Stayveer, Tracleer, SID50112694, BOSENTAN, bosentan

Parent form; salt/anhydrous children: CHEMBL175616

Patent coverage: 3,733 distinct patent families (16,499 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 16,490 (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
EDNRA	ETA receptor	Antagonist	7.2	0.1%	P25101
EDNRB	ETB receptor	Antagonist	7.1	0%	P24530

Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Nuclear receptor ROR-gamma, 4’-phosphopantetheinyl transferase ffp, ATP-binding cassette sub-family C member 4, Endothelin receptor type B, Bile salt export pump, Endothelin-1 receptor, Oxysterols receptor LXR-alpha, Nuclear receptor subfamily 1 group I member 2, Endothelin-1 receptor, Deoxyhypusine synthase.

Bioactivity

ChEMBL activities: 43 potent at pChembl ≥ 5 of 57 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
EDNRA	8.44	Ki	3.67	nM	CHEMBL_ACT_26274376
P26684	8.33	IC50	4.7	nM	CHEMBL_ACT_15166369
EDNRA	8.33	IC50	4.7	nM	CHEMBL_ACT_16762693
EDNRA	8.33	IC50	4.7	nM	CHEMBL_ACT_26154590
P26684	8.19	Ki	6.5	nM	CHEMBL_ACT_172354
EDNRA	8.19	Ki	6.5	nM	CHEMBL_ACT_172677
EDNRA	8.19	Ki	6.5	nM	CHEMBL_ACT_26274398
Q29010	8.12	IC50	7.5	nM	CHEMBL_ACT_250599
EDNRA	8.1	IC50	8	nM	CHEMBL_ACT_668224
EDNRA	8.1	Ki	8	nM	CHEMBL_ACT_932542
EDNRA	8.08	IC50	8.4	nM	CHEMBL_ACT_16441921
EDNRA	8.05	IC50	8.9	nM	CHEMBL_ACT_10964029
EDNRA	7.54	AC50	28.6	nM	CHEMBL_ACT_25178942
P26684	7.4	Kd	39.81	nM	CHEMBL_ACT_19405674
EDNRA	7.4	IC50	40	nM	CHEMBL_ACT_731006
EDNRA	7.35	IC50	45	nM	CHEMBL_ACT_12091156
EDNRA	7.35	IC50	45	nM	CHEMBL_ACT_19405691
EDNRA	7.35	IC50	45	nM	CHEMBL_ACT_19441186
P26684	7.3	Kd	50.12	nM	CHEMBL_ACT_668228
P26684	7.14	Kd	72.44	nM	CHEMBL_ACT_731008
EDNRA	7.1	IC50	80	nM	CHEMBL_ACT_19405654
EDNRA	7.1	IC50	80	nM	CHEMBL_ACT_25048366
EDNRA	7.1	IC50	80	nM	CHEMBL_ACT_668223
EDNRB	7.1	Ki	80	nM	CHEMBL_ACT_932544
P21451	7.02	IC50	95	nM	CHEMBL_ACT_15166363
EDNRB	7.02	IC50	95	nM	CHEMBL_ACT_16762694
EDNRB	6.82	IC50	150	nM	CHEMBL_ACT_19405669
EDNRB	6.82	IC50	150	nM	CHEMBL_ACT_668225
EDNRB	6.7	IC50	202	nM	CHEMBL_ACT_12091100
EDNRB	6.7	IC50	202	nM	CHEMBL_ACT_19405692

Target pathways

Aggregated over 2 target gene(s): EDNRA, EDNRB.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	2	EDNRA, EDNRB
G alpha (q) signalling events	2	EDNRA, EDNRB
Transcriptional and post-translational regulation of MITF-M expression and activity	1	EDNRB

Dominant GO biological processes

GO term	Targets
regulation of heart rate	2
signal transduction	2
G protein-coupled receptor signaling pathway	2
phospholipase C-activating G protein-coupled receptor signaling pathway	2
positive regulation of cytosolic calcium ion concentration	2
regulation of blood pressure	2
gene expression	2
heparin proteoglycan metabolic process	2
vasoconstriction	2
positive regulation of canonical NF-kappaB signal transduction	2
developmental pigmentation	2
enteric nervous system development	2
sodium ion homeostasis	2
canonical Wnt signaling pathway	2
establishment of endothelial barrier	2

Indications & clinical

Indications

27 indications (6 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
pulmonary arterial hypertension	4	MONDO:0015924	EFO:0001361
systemic sclerosis	4	MONDO:0005100	EFO:0000717
congenital heart disease	4	MONDO:0005453	EFO:0005207
hypertensive disorder	4	MONDO:0005044	EFO:0000537
pulmonary hypertension	4	MONDO:0005149	MONDO:0005149
idiopathic pulmonary fibrosis	3	MONDO:0800504	EFO:0000768
anterior ischemic optic neuropathy	3	MONDO:0006649	EFO:1000809
persistent fetal circulation syndrome	3	MONDO:0022430	EFO:1001103
Eisenmenger syndrome	3	MONDO:0019944	EFO:0009200
ulcer disease	3	MONDO:0043839	MONDO:0043839
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
atrial septal defect	3	MONDO:0006664	MONDO:0007172
chronic obstructive pulmonary disease	2	MONDO:0005002	EFO:0000341
melanoma	2	MONDO:0005105	EFO:0000756
cirrhosis of liver	2	MONDO:0005155	EFO:0001422
hypoplastic left heart syndrome	2	MONDO:0004933	MONDO:0004933
asthma	2	MONDO:0004979	MONDO:0004979
Hermansky-Pudlak syndrome	2	MONDO:0019312	MONDO:0019312
congestive heart failure	1	MONDO:0005009	EFO:0000373
mitral valve stenosis	1	MONDO:0005852	EFO:0007372
diabetes mellitus	1	MONDO:0005015	EFO:0000400
exocrine pancreatic carcinoma	1	MONDO:0005192	EFO:0002618
neoplasm	1	MONDO:0005070	EFO:0000616
glaucoma	1	MONDO:0005041	MONDO:0005041
sleep apnea syndrome	0	MONDO:0005296	EFO:0003877

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 95.

Phase distribution

Phase	Trials
PHASE3	25
PHASE2	19
PHASE4	15
PHASE1	14
Not specified	12
PHASE2/PHASE3	5
EARLY_PHASE1	3
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00082186	PHASE4	COMPLETED	The Effect of Tracleer® on Male Fertility
NCT00266162	PHASE4	COMPLETED	Bosentan in Treatment of Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00317486	PHASE4	COMPLETED	Effects of Tracleer (Bosentan) on Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00595049	PHASE4	COMPLETED	Pulmonary Artery Remodelling With Bosentan
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00637065	PHASE4	UNKNOWN	Bosentan in Pulmonary Hypertension in Interstitial Lung Disease Treatment Study
NCT00679068	PHASE4	TERMINATED	Effects of Bosentan on Respiratory Mechanics
NCT01395732	PHASE4	COMPLETED	Bosentan in Systemic Sclerosis
NCT01449253	PHASE4	UNKNOWN	Comparison of Efficacy Different Treatment Regimens in Pulmonary Hypertension Secondary to Lung Disease and or Hypoxia
NCT01779596	PHASE4	COMPLETED	ET-blockade and Exercise Induced Blood Flow in T2DM
NCT01779609	PHASE4	COMPLETED	ET-blockade and Exercise-induced Vascular Adaptations in T2DM
NCT02480335	PHASE4	COMPLETED	The Clinical And Subclinical Effects on Arterial Stiffness of Bosentan in Patients With Systemic Sclerosis
NCT00070590	PHASE2/PHASE3	COMPLETED	Efficacy and Safety of Oral Bosentan in Pulmonary Fibrosis Associated With Scleroderma
NCT00071461	PHASE2/PHASE3	COMPLETED	Efficacy and Safety of Oral Bosentan in Patients With Idiopathic Pulmonary Fibrosis
NCT00077584	PHASE3	COMPLETED	Efficacy and Safety of Oral Bosentan on Healing/Prevention of Digital (Finger) Ulcers in Patients With Scleroderma
NCT00091715	PHASE3	COMPLETED	Efficacy and Safety of Oral Bosentan in Pulmonary Arterial Hypertension Class II
NCT00302211	PHASE3	TERMINATED	The VISION Trial: Ventavis Inhalation With Sildenafil to Improve and Optimize Pulmonary Arterial Hypertension
NCT00303004	PHASE3	COMPLETED	Combination Treatment With Bosentan and Sildenafil to Patients With Eisenmengers Syndrome
NCT00310830	PHASE3	TERMINATED	Efficacy and Safety of Bosentan in Sickle Cell Disease (SCD) Patients With Pulmonary Arterial Hypertension (PAH)
NCT00313196	PHASE3	TERMINATED	Efficacy and Safety of Bosentan in Sickle Cell Disease (SCD) Patients Diagnosed With Pulmonary Hypertension (PH)
NCT00313222	PHASE3	COMPLETED	Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension
NCT00319020	PHASE3	COMPLETED	Bosentan in Children With Pulmonary Arterial Hypertension Extension Study
NCT00319033	PHASE2/PHASE3	COMPLETED	Open-label Study With Bosentan in Interstitial Lung Disease
NCT00319111	PHASE3	COMPLETED	Bosentan in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
NCT00319267	PHASE3	COMPLETED	Bosentan in Children With Pulmonary Arterial Hypertension
NCT00319696	PHASE3	COMPLETED	Bosentan in Digital Ulcers
NCT00360087	PHASE3	TERMINATED	A Study of Patients Having Pulmonary Hypertension Associated With Sickle Cell Disease and Completing an ASSET Study
NCT00391443	PHASE3	COMPLETED	BUILD 3: Bosentan Use in Interstitial Lung Disease
NCT00581607	PHASE2/PHASE3	COMPLETED	Double Blind, Randomized Trial of Bosentan for Sarcoidosis Associated Pulmonary Hypertension
NCT00631475	PHASE3	COMPLETED	Open Label Extension Study in Patients With Idiopathic Pulmonary Fibrosis Who Completed Protocol AC-052-321/ BUILD 3 / NCT00391443
NCT00638131	PHASE3	TERMINATED	Bosentan Use in Patients With Diabetic Nephropathy
NCT00820352	PHASE3	COMPLETED	Safety and Efficacy of Bosentan in Patients With Diastolic Heart Failure and Secondary Pulmonary Hypertension
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01218607	PHASE3	COMPLETED	Bosentan for Mild Pulmonary Vascular Disease in Asd Patients.
NCT01223352	PHASE3	COMPLETED	Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension
NCT01338415	PHASE3	COMPLETED	FUTURE 3 Study Extension
NCT01352065	PHASE2/PHASE3	COMPLETED	Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 13 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

50 molecules share ≥1 primary target. Top 50 by shared-target count:

Molecule	Source	Status	Shared targets
AMBRISENTAN	ChEMBL	Phase 4 (approved)	EDNRA, EDNRB
APROCITENTAN	ChEMBL	Phase 4 (approved)	EDNRA, EDNRB
MACITENTAN	ChEMBL	Phase 4 (approved)	EDNRA, EDNRB
SITAXENTAN	ChEMBL	Phase 4 (approved)	EDNRA, EDNRB
SULFISOXAZOLE	ChEMBL	Phase 4 (approved)	EDNRA, EDNRB
ATRASENTAN	ChEMBL	Phase 3	EDNRA, EDNRB
AVOSENTAN	ChEMBL	Phase 3	EDNRA, EDNRB
CLAZOSENTAN	ChEMBL	Phase 3	EDNRA, EDNRB
DARUSENTAN	ChEMBL	Phase 3	EDNRA, EDNRB
TEZOSENTAN	ChEMBL	Phase 3	EDNRA, EDNRB
ENDOTHELIN	ChEMBL	Phase 2	EDNRA, EDNRB
ENRASENTAN	ChEMBL	Phase 2	EDNRA, EDNRB
FELOPRENTAN	ChEMBL	Phase 2	EDNRA, EDNRB
Dihydroergotamine	PubChem	Approved	EDNRA, EDNRB
Fidaxomicin	PubChem	Approved	EDNRA, EDNRB
Propoxyphene	PubChem	Approved	EDNRA, EDNRB
Pyrazinamide	PubChem	Approved	EDNRA, EDNRB
SPARSENTAN	ChEMBL + PubChem	Phase 4 (approved)	EDNRA
ACYCLOVIR	ChEMBL	Phase 4 (approved)	EDNRA
AMIODARONE	ChEMBL	Phase 4 (approved)	EDNRA
ENOXACIN	ChEMBL	Phase 4 (approved)	EDNRA
FLUOXETINE	ChEMBL	Phase 4 (approved)	EDNRA
GRAMICIDIN	ChEMBL	Phase 4 (approved)	EDNRA
IRBESARTAN	ChEMBL	Phase 4 (approved)	EDNRA
MAZINDOL	ChEMBL	Phase 4 (approved)	EDNRB
MELOXICAM	ChEMBL	Phase 4 (approved)	EDNRA
MODAFINIL	ChEMBL	Phase 4 (approved)	EDNRB
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	EDNRA
PIOGLITAZONE	ChEMBL	Phase 4 (approved)	EDNRA
SULFATHIAZOLE	ChEMBL	Phase 4 (approved)	EDNRA
SUNITINIB	ChEMBL	Phase 4 (approved)	EDNRA
EXISULIND	ChEMBL	Phase 3	EDNRA
ZIBOTENTAN	ChEMBL	Phase 3	EDNRA
BQ-123	ChEMBL	Phase 2	EDNRA
EDONENTAN	ChEMBL	Phase 2	EDNRA
FANDOSENTAN	ChEMBL	Phase 2	EDNRA
Aclidinium Bromide	PubChem	Approved	EDNRB
Afatinib	PubChem	Approved	EDNRA
Alogliptin	PubChem	Approved	EDNRB
Apixaban	PubChem	Approved	EDNRA
Belzutifan	PubChem	Approved	EDNRB
Binimetinib	PubChem	Approved	EDNRA
chenodiol	PubChem	Approved	EDNRA
Desloratadine	PubChem	Approved	EDNRB
Fulvestrant	PubChem	Approved	EDNRA
Imipenem	PubChem	Approved	EDNRA
Methotrexate	PubChem	Approved	EDNRB
Olmesartan Medoxomil	PubChem	Approved	EDNRB
Tafamidis	PubChem	Approved	EDNRA
Tiotropium Bromide Monohydrate	PubChem	Approved	EDNRB