Darusentan

Summary

Darusentan (CHEMBL23261) is a phase-3 clinical-stage small molecule targeting EDNRA; indicated across 1 condition including hypertensive disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (EDNRA)
• Indications: 1 condition
• Clinical trials: 6
• Chemistry: 410.4 Da · C22H22N2O6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL23261
Name	Darusentan
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	177236
Molecular formula	C22H22N2O6
Molecular weight	410.4
InChIKey	FEJVSJIALLTFRP-LJQANCHMSA-N

SMILES: COC1=CC(=NC(=N1)O[C@H](C(=O)O)C(C2=CC=CC=C2)(C3=CC=CC=C3)OC)OC

IUPAC name: (2S)-2-(4,6-dimethoxypyrimidin-2-yl)oxy-3-methoxy-3,3-diphenylpropanoic acid

Also known as: Darusentan, HMR-4005, Lu-135252, LU-135252, SID170466416, DARUSENTAN, darusentan

Patent coverage: 150 distinct patent families (357 SureChEMBL compound mentions), from 1 matched compound structure(s). 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	8.9	0.1%	P25101

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Endothelin receptor type B, Endothelin-1 receptor, 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	9.1	IC50	0.8	nM	CHEMBL_ACT_826680
P26684	8.22	Ki	6	nM	CHEMBL_ACT_171132
EDNRA	8.22	Ki	6	nM	CHEMBL_ACT_19405750
EDNRB	7.8	IC50	16	nM	CHEMBL_ACT_826681
EDNRB	6.43	Ki	371	nM	CHEMBL_ACT_19405785

Target pathways

Aggregated over 1 target gene(s): EDNRA.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	1	EDNRA
G alpha (q) signalling events	1	EDNRA

Dominant GO biological processes

GO term	Targets
mitotic cell cycle	1
branching involved in blood vessel morphogenesis	1
response to hypoxia	1
in utero embryonic development	1
blood vessel remodeling	1
response to amphetamine	1
regulation of heart rate	1
glomerular filtration	1
cardiac chamber formation	1
left ventricular cardiac muscle tissue morphogenesis	1
atrial cardiac muscle tissue development	1
cardiac neural crest cell migration involved in outflow tract morphogenesis	1
noradrenergic neuron differentiation	1
intracellular calcium ion homeostasis	1
smooth muscle contraction	1

Indications & clinical

Indications

1 indication (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
hypertensive disorder	3	MONDO:0005044	EFO:0000537

Clinical trials

Total trials: 6.

Phase distribution

Phase	Trials
PHASE3	4
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00330369	PHASE3	COMPLETED	DORADO - Fixed Doses of Darusentan as Compared to Placebo in Resistant Hypertension
NCT00353574	PHASE3	TERMINATED	DORADO-EX: Long-Term Safety Extension Study to the Phase 3 DORADO Study (Protocol DAR-311) of Darusentan in Resistant Hypertension
NCT00389675	PHASE3	TERMINATED	DORADO-AC-EX - A Long-Term Safety Extension Study to the Phase 3 DORADOC-AC Study (Protocol DAR-312) of Darusentan in Resistant Hypertension
NCT00389779	PHASE3	COMPLETED	DORADO-AC - Optimized Doses of Darusentan as Compared to an Active Control in Resistant Hypertension
NCT00364026	PHASE2	COMPLETED	A Clinical Study to Evaluate the Effects of Darusentan on Safety and Efficacy in Subjects With Resistant Systolic Hypertension Receiving Combination Therapy With Three or More Blood Pressure Lowering Drugs
NCT00738049	PHASE2	COMPLETED	Darusentan Effect on PET Uptake Heterogeneity

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.

41 molecules share ≥1 primary target. Top 41 by shared-target count:

Molecule	Source	Status	Shared targets
BOSENTAN	ChEMBL + PubChem	Phase 4 (approved)	EDNRA
SPARSENTAN	ChEMBL + PubChem	Phase 4 (approved)	EDNRA
ACYCLOVIR	ChEMBL	Phase 4 (approved)	EDNRA
AMBRISENTAN	ChEMBL	Phase 4 (approved)	EDNRA
AMIODARONE	ChEMBL	Phase 4 (approved)	EDNRA
APROCITENTAN	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
MACITENTAN	ChEMBL	Phase 4 (approved)	EDNRA
MELOXICAM	ChEMBL	Phase 4 (approved)	EDNRA
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	EDNRA
PIOGLITAZONE	ChEMBL	Phase 4 (approved)	EDNRA
SITAXENTAN	ChEMBL	Phase 4 (approved)	EDNRA
SULFATHIAZOLE	ChEMBL	Phase 4 (approved)	EDNRA
SULFISOXAZOLE	ChEMBL	Phase 4 (approved)	EDNRA
SUNITINIB	ChEMBL	Phase 4 (approved)	EDNRA
ATRASENTAN	ChEMBL	Phase 3	EDNRA
AVOSENTAN	ChEMBL	Phase 3	EDNRA
CLAZOSENTAN	ChEMBL	Phase 3	EDNRA
EXISULIND	ChEMBL	Phase 3	EDNRA
TEZOSENTAN	ChEMBL	Phase 3	EDNRA
ZIBOTENTAN	ChEMBL	Phase 3	EDNRA
BQ-123	ChEMBL	Phase 2	EDNRA
EDONENTAN	ChEMBL	Phase 2	EDNRA
ENDOTHELIN	ChEMBL	Phase 2	EDNRA
ENRASENTAN	ChEMBL	Phase 2	EDNRA
FANDOSENTAN	ChEMBL	Phase 2	EDNRA
FELOPRENTAN	ChEMBL	Phase 2	EDNRA
Afatinib	PubChem	Approved	EDNRA
Apixaban	PubChem	Approved	EDNRA
Binimetinib	PubChem	Approved	EDNRA
chenodiol	PubChem	Approved	EDNRA
Dihydroergotamine	PubChem	Approved	EDNRA
Fidaxomicin	PubChem	Approved	EDNRA
Fulvestrant	PubChem	Approved	EDNRA
Imipenem	PubChem	Approved	EDNRA
Propoxyphene	PubChem	Approved	EDNRA
Pyrazinamide	PubChem	Approved	EDNRA
Tafamidis	PubChem	Approved	EDNRA