Clazosentan

Summary

Clazosentan (CHEMBL109648) is a phase-3 clinical-stage small molecule (ATC C04AX33) targeting EDNRA and EDNRB; indicated across 2 conditions including subarachnoid hemorrhage and cardiovascular disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: C04AX33
• Targets: 2 (EDNRA, EDNRB)
• Indications: 2 conditions
• Clinical trials: 7
• Chemistry: 577.6 Da · C25H23N9O6S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL109648
Name	Clazosentan
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	6433095
ATC	C04AX33
Molecular formula	C25H23N9O6S
Molecular weight	577.6
InChIKey	LFWCJABOXHSRGC-UHFFFAOYSA-N

SMILES: CC1=CN=C(C=C1)S(=O)(=O)NC2=C(C(=NC(=N2)C3=CC(=NC=C3)C4=NNN=N4)OCCO)OC5=CC=CC=C5OC

IUPAC name: N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2H-tetrazol-5-yl)-4-pyridinyl]pyrimidin-4-yl]-5-methylpyridine-2-sulfonamide

Also known as: ACT-108475, Axv-034, AXV-034343, AXV-343434, Clazosentan, Pivlaz, VML-588, clazosentan, CLAZOSENTAN

Parent form; salt/anhydrous children: CHEMBL5314590

Patent coverage: 107 distinct patent families (244 SureChEMBL compound mentions), from 6 matched compound structure(s). One matched structure accounts for 174 (71%) 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	9.5	0.1%	P25101
EDNRB	ETB receptor	Antagonist	6.76	0%	P24530

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Endothelin receptor type B, Endothelin-1 receptor.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
EDNRA	9.89	Ki	0.13	nM	CHEMBL_ACT_26274395
EDNRA	9.89	Ki	0.13	nM	CHEMBL_ACT_493821
EDNRA	8.77	IC50	1.7	nM	CHEMBL_ACT_19405687
EDNRB	6.76	IC50	175	nM	CHEMBL_ACT_19405665
EDNRB	6.76	Ki	175	nM	CHEMBL_ACT_493822

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

2 indications (0 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
subarachnoid hemorrhage	3	MONDO:0005099	EFO:0000713
cardiovascular disorder	3	MONDO:0004995	EFO:0000319

Clinical trials

Total trials: 7.

Phase distribution

Phase	Trials
PHASE3	3
PHASE2	2
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00558311	PHASE3	COMPLETED	Clazosentan in Reducing Vasospasm-related Morbidity and All-cause Mortality in Adult Patients With Aneurysmal Subarachnoid Hemorrhage Treated by Surgical Clipping
NCT00940095	PHASE3	TERMINATED	Clazosentan in Aneurysmal Subarachnoid Hemorrhage
NCT03585270	PHASE3	COMPLETED	Clinical Research Study With Clazosentan to Evaluate Its Effects on Preventing Complications Due to the Narrowing of the Blood Vessels (Vasospasm) in the Brain, Caused by Bleeding Onto the Surface of the Brain
NCT00111085	PHASE2	COMPLETED	Clazosentan in Preventing the Occurrence of Cerebral Vasospasm Following an Aneurysmal Subarachnoid Hemorrhage (aSAH)
NCT02560532	PHASE2	COMPLETED	Evaluation of the Efficacy and Safety of Clazosentan in Reversing Cerebral Vasospasm in Adult Subjects With Aneurysmal Subarachnoid Hemorrhage
NCT03596294	PHASE1	COMPLETED	A Study in Healthy Male Subjects to Investigate Whether Administration of Rifampicin Can Affect the Fate of Clazosentan in the Body of Clazosentan
NCT03657446	PHASE1	COMPLETED	A Study in Healthy Subjects to Investigate Whether Administration of Clazosentan Can Affect Normal Heart Function

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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
BOSENTAN	ChEMBL + PubChem	Phase 4 (approved)	EDNRA, EDNRB
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
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