Ambrisentan

Summary

Ambrisentan (CHEMBL1111) is an approved small molecule (ATC C02KX02) targeting EDNRA and EDNRB; indicated across 11 conditions including pulmonary arterial hypertension and hypertensive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C02KX02
• Targets: 2 (EDNRA, EDNRB)
• Indications: 11 conditions
• Clinical trials: 56
• Chemistry: 378.4 Da · C22H22N2O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1111
Name	Ambrisentan
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	6918493
ATC	C02KX02
Molecular formula	C22H22N2O4
Molecular weight	378.4
InChIKey	OUJTZYPIHDYQMC-LJQANCHMSA-N

SMILES: CC1=CC(=NC(=N1)O[C@H](C(=O)O)C(C2=CC=CC=C2)(C3=CC=CC=C3)OC)C

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

Also known as: Ambrisentan, Ambrisentan mylan, GSK-1325760, GSK-1325760A, GSK1325760, GSK1325760A, Letairis, LU-208075, Volibris, ambrisentan, AMBRISENTAN, SID170465143

Patent coverage: 1,674 distinct patent families (7,009 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	7.1	0.1%	P25101
EDNRB	ETB receptor	Antagonist	5.92	0%	P24530

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Endothelin receptor type B, Endothelin receptor, Voltage-gated potassium channel, IKs; KCNQ1(Kv7.1)/KCNE1(MinK), Endothelin-1 receptor, Nuclear receptor subfamily 1 group I member 2.

Bioactivity

ChEMBL activities: 6 potent at pChembl ≥ 5 of 9 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
EDNRA	9	IC50	1	nM	CHEMBL_ACT_19405751
EDNRA	7.66	IC50	21.7	nM	CHEMBL_ACT_805154
P21451	7.09	Kd	81.28	nM	CHEMBL_ACT_805156
EDNRB	6.71	IC50	195	nM	CHEMBL_ACT_19405786
EDNRB	5.92	IC50	1190	nM	CHEMBL_ACT_805155
P21451	5.63	Kd	2344	nM	CHEMBL_ACT_805157

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

11 indications (4 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
hypertensive disorder	4	MONDO:0005044	EFO:0000537
pulmonary hypertension	4	MONDO:0005149	MONDO:0005149
idiopathic pulmonary fibrosis	3	MONDO:0800504	EFO:0000768
vascular disorder	3	MONDO:0005385	EFO:0004264
altitude sickness	2	MONDO:0006625	EFO:1000782
hypoplastic left heart syndrome	2	MONDO:0004933	MONDO:0004933
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096
asthma	2	MONDO:0004979	MONDO:0004979
sickle cell disease	1	MONDO:0011382	MONDO:0011382

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

Clinical trials

Total trials: 56.

Phase distribution

Phase	Trials
PHASE3	16
PHASE2	11
Not specified	10
PHASE4	9
PHASE2/PHASE3	4
PHASE1	4
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07030894	PHASE4	RECRUITING	Nefecon and Ambrisentan in IgA Nephropathy
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00840463	PHASE4	TERMINATED	Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan
NCT01051960	PHASE4	COMPLETED	Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01338636	PHASE4	COMPLETED	An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Participants With Exercise-Induced Pulmonary Arterial Hypertension (PAH)
NCT01971580	PHASE4	COMPLETED	The Effects of Ambrisentan on Exercise Capacity in Fontan Patients
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT03309592	PHASE4	WITHDRAWN	Efficacy and Safety of Combination Ambrisentan and Tadalafil in Patients With Portopulmonary Hypertension
NCT07245680	PHASE3	RECRUITING	COMMODITIES Trial: Initial Dual Oral Therapy vs Monotherapy in PAH With Cardiovascular Comorbidities
NCT00091598	PHASE3	COMPLETED	ARIES - Ambrisentan in Patients With Moderate to Severe Pulmonary Arterial Hypertension (PAH)
NCT00380068	PHASE3	COMPLETED	Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension
NCT00423202	PHASE3	COMPLETED	A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess Safety and Efficacy of Ambrisentan in Subjects With Pulmonary Arterial Hypertension.
NCT00423748	PHASE3	COMPLETED	Study to Assess Safety and Efficacy of Ambrisentan in Subjects With Pulmonary Arterial Hypertension.
NCT00554619	PHASE3	COMPLETED	A Study to Evaluate GSK1325760A - a Long-Term Extension Study
NCT00578786	PHASE3	COMPLETED	A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 (NCT00423748) or AMB-321 (NCT00423202)
NCT00768300	PHASE3	TERMINATED	(ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF
NCT00777920	PHASE3	COMPLETED	Study of Ambrisentan in Participants With Pulmonary Hypertension
NCT00851929	PHASE2/PHASE3	COMPLETED	Ambrisentan (Letairis) for Sarcoidosis Associated Pulmonary Hypertension
NCT00879229	PHASE3	TERMINATED	ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis
NCT01178073	PHASE3	COMPLETED	A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
NCT01224210	PHASE3	COMPLETED	Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial
NCT01352065	PHASE2/PHASE3	COMPLETED	Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration
NCT01808313	PHASE3	COMPLETED	Efficacy Study of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension (PAH)
NCT01884675	PHASE3	TERMINATED	Ambrisentan for Inoperable Chronic Thromboembolic Pulmonary Hypertension.
NCT01894022	PHASE3	TERMINATED	A Open Label Study to Assess the Long-term Safety, Tolerability and Efficacy of Ambrisentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
NCT01902758	PHASE2/PHASE3	COMPLETED	Drug Combination on Exercise Performance at High Altitude
NCT04393246	PHASE2/PHASE3	COMPLETED	mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Experimental Drugs and Mechanisms
NCT05437224	PHASE3	COMPLETED	Efficacy and Safety Study of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension
NCT06256432	PHASE2	ACTIVE_NOT_RECRUITING	Endothelin Receptor Antagonism With Ambrisentan to Treat Hepatorenal Syndrome
NCT00423592	PHASE2	COMPLETED	Phase 2 Study of Ambrisentan for Liver Function Test Rescue in Pulmonary Arterial Hypertension
NCT00424021	PHASE2	COMPLETED	Phase 2 Extension Study of Ambrisentan in Pulmonary Arterial Hypertension
NCT00540436	PHASE2	COMPLETED	Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension
NCT01342952	PHASE2	COMPLETED	Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529
NCT01617746	PHASE2	UNKNOWN	Examination of the Bronchoprotective Effect of Endothelin Receptor Blockade in Asthma
NCT01733095	PHASE1/PHASE2	WITHDRAWN	Ambrisentan for Treatment of Portopulmonary Hypertension
NCT02080637	PHASE2	COMPLETED	Ambrisentan in Single Ventricle
NCT02290613	PHASE2	COMPLETED	Early Treatment of Borderline Pulmonary Arterial Hypertension Associated With Systemic Sclerosis (SSc-APAH)
NCT03827200	PHASE2	TERMINATED	A Study Evaluating the Utility of Ambrisentan in Lowering Portal Pressure in Patients With Liver Cirrhosis
NCT04450095	PHASE2	UNKNOWN	Effects of Endothelin Receptor Antagonist on Ischemic Kidney Injury During Nephron Sparing Surgery

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 7 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
BOSENTAN	ChEMBL + PubChem	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