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Protein / target

Endothelin receptor type B

Encoded byEDNRBP24530Homo sapiensSwiss-Prot
UniProt: P24530Ensembl: ENSG00000136160HGNC: HGNC:3180NCBI Gene: 1910
Clinically validated
Therapeutic maturity
6
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Type 1 angiotensin receptor binding

Strongest disease association

Hirschsprung disease

Via encoding gene EDNRB · Genetic literature evidence · score 0.83

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Non-specific receptor for endothelin 1, 2, and 3.

View complete UniProt function annotation

Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Subcellular location

Cell membrane
Domains and Gene Ontology detail (49)

Gene Ontology

  • Cnuclear membrane
  • Cplasma membrane
  • Fendothelin receptor activity
  • Fpeptide hormone binding
  • Ftype 1 angiotensin receptor binding
  • Paldosterone metabolic process
  • Pcalcium ion transmembrane transport
  • Pcalcium-mediated signaling
  • Pcanonical Wnt signaling pathway
  • Pcell surface receptor signaling pathway
  • Pcellular response to lipopolysaccharide
  • PcGMP biosynthetic process

442 aa · 50 kDa · 3 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Ion channel gatingGOCell proliferation & survivalGOCell migrationGOMetabolic enzyme activityGOTranscriptional regulationGO
View supporting evidence

Ion channel gating

  • ·calcium ion transmembrane transport

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Cell migration

  • ·macrophage chemotaxis

Metabolic enzyme activity

  • ·aldosterone metabolic process
  • ·heparin proteoglycan metabolic process
  • ·negative regulation of protein metabolic process

Transcriptional regulation

  • ·gene expression
  • ·negative regulation of transcription by RNA polymerase II

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

3 medicines · 3 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Hypertension3 medicines
ambrisentanmacitentansitaxentan
Familial Primary Pulmonary Hypertension2 medicines
ambrisentanmacitentan
Hypertension, Pulmonary2 medicines
ambrisentanmacitentan

6 medicines meet Open Targets' target-level approved-medicine definition; the 3 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

3

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

sitaxentan
ApprovedAntagonist

Endothelin receptor, ET-A/ET-B antagonist

Indicated for Hypertension

Acts on a complex — shared with EDNRA · 1 of 2 recorded protein targets — narrow recorded profile

ambrisentan
ApprovedAntagonist

Endothelin receptor, ET-A/ET-B antagonist

Indicated for Familial Primary Pulmonary Hypertension, Hypertension, Hypertension, Pulmonary

Acts on a complex — shared with EDNRA · 1 of 2 recorded protein targets — narrow recorded profile

macitentan
ApprovedAntagonist

Endothelin receptor, ET-A/ET-B antagonist

Indicated for Familial Primary Pulmonary Hypertension, Hypertension, Hypertension, Pulmonary

Acts on a complex — shared with EDNRA · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene EDNRB

Gene-level evidence surfaced through the gene EDNRBthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Pulmonary arterial hypertension
0.77Well supported

Clinical evidence dominant · Open Targets 0.62

Hirschsprung disease
0.77Well supported

Genetic literature evidence dominant · Open Targets 0.55

Hypertension, Pulmonary
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

Hypertension
0.71Moderately supported

Clinical evidence dominant · Open Targets 0.57

Scleroderma, Systemic
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.56

View evidence synthesis (5)
Pulmonary arterial hypertensionWell supported
0.77
agreement 0.61–0.92
Clinical88%Literature12%

Open Targets aggregate 0.62 · 2 independent evidence families

Hirschsprung diseaseWell supported
0.77
agreement 0.64–0.89
Genetic literature67%Animal model29%Literature4%Geneticdup

Open Targets aggregate 0.55 · 3 independent evidence families · 1 not counted as duplicate

Hypertension, PulmonaryModerately supported
0.73
agreement 0.57–0.89
Clinical97%Literature3%

Open Targets aggregate 0.59 · 2 independent evidence families

HypertensionModerately supported
0.71
agreement 0.55–0.86
Clinical90%Literature10%

Open Targets aggregate 0.57 · 2 independent evidence families

Scleroderma, SystemicModerately supported
0.70
agreement 0.55–0.85
Clinical94%Literature6%

Open Targets aggregate 0.56 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Pulmonary arterial hypertension0.62
Hypertension, Pulmonary0.59
Hypertension0.57
Scleroderma, Systemic0.56
Hirschsprung disease0.55

Drug development

10 compounds recorded · 6 approved · 4 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
BOSENTANApproval
AMBRISENTANApproval
APROCITENTANApproval
SITAXENTANApproval
MACITENTANApproval
RG-7636Phase 1
DARUSENTANPhase 3
ENRASENTANPhase 2
TEZOSENTANPhase 3
SITAXENTAN SODIUMApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalities — Supported

Phase 1 Clinical support this modality.

View underlying tractability evidence (11)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Half-life DataPR · Small Molecule BinderOC · Phase 1 Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

decreased intestinal transitLynch et al. (2017)decreased gastric emptyingLynch et al. (2017)increased then decreased heart rateLynch et al. (2017)decreased urine excretionLynch et al. (2017)decreased painLynch et al. (2017)cell proliferationLynch et al. (2017)receptor bindingToxCastincreased blood pressureLynch et al. (2017)left ventricular hypertrophyLynch et al. (2017)cardiovascular malformationsLynch et al. (2017)decreased then increased blood pressureLynch et al. (2017)bronchoconstrictionLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Comparison of Initial Dual Oral COMbination Therapy to MOnotherapy in Pulmonary Arterial Hypertension With Cardiovascular comorbiDITIESPHASE3

RECRUITING · via ambrisentan · NCT07245680

Effects of Combination Medical Therapy Followed by Balloon Pulmonary Angioplasty on Right Ventricular-PA Coupling and Hemodynamics in Chronic Thromboembolic Pulmonary HypertensionPHASE3

RECRUITING · via macitentan · NCT05140525

A Prospective, Open-label, Platform Study for Long-term Follow-up of Participants Using Study Intervention in Pulmonary Hypertension Parent StudiesPHASE3

RECRUITING · via macitentan · NCT05179876

A Phase 3, Prospective, Multicenter, Double-blind, Double-dummy, Randomized, Active-controlled, Parallel-group, Group-sequential, Adaptive, Event-driven Study to Compare Efficacy, Safety, and Tolerability of Macitentan 75 mg Versus Macitentan 10 mg in Patients With Pulmonary Arterial Hypertension, Followed by an Open-label Treatment Period With Macitentan 75 mgPHASE3

ACTIVE_NOT_RECRUITING · via macitentan · NCT04273945

View all trials (26)
A Multi-Centre, Randomised, Open-Label, Phase II Study of Ambrisentan in Patients With Hepatorenal SyndromePHASE2

ACTIVE_NOT_RECRUITING · via ambrisentan · NCT06256432

Ambrisentan for the Treatment of Early-Stage Low-Risk Pulmonary Arterial Hypertension: A Multicenter, Randomized, Double-Blind, Placebo-Controlled ALEPH TrialNA

NOT_YET_RECRUITING · via ambrisentan · NCT06987097

A Multicenter, Randomized, Controlled, Double-blind, and Non-inferiority Clinical Trial to Compare the Efficacy of Sequential to Initial Combination Therapy in Patients With Pulmonary Arterial HypertensionNA

RECRUITING · via ambrisentan · NCT06968962

Impact of Endothelin-1 on the Development of Cardiac Allograft Vasculopathy in Heart Transplant Recipients: Endothelin Receptor Antagonism and Vasomotor FunctionPHASE4

COMPLETED · via macitentan · NCT05373108

Potential Therapy With MACITENTAN in the Treatment of Chronic Lung Allograft Dysfunction (CLAD) After Lung TransplantationPHASE4

WITHDRAWN · via macitentan · NCT02893176

A Safety and Clinical Efficacy Study Measuring Echocardiographic Composite Comparing Ambrisentan (Letairis®) After a Switch From Bosentan (Tracleer®) or Macintentan (Opsumit®) in Treatment of Pulmonary Arterial Hypertension (PAH)PHASE4

TERMINATED · via ambrisentan · NCT02885012

Prospective, Multicenter, Open-label Study Evaluating the Effects of First-line Oral Combination Therapy of Macitentan and Tadalafil in Patients With Newly Diagnosed Pulmonary Arterial Hypertension (OPTIMA).PHASE4

TERMINATED · via macitentan · NCT02968901

A Randomized, Double-blind, Placebo-controlled, Prospective, Multicenter, Parallel Group Study to Assess the Safety and Efficacy of Macitentan in Patients With Portopulmonary HypertensionPHASE4

COMPLETED · via macitentan · NCT02382016

A Prospective, Multicenter, Single-arm, Open-label, Phase 4 Study to Evaluate the Effects of Macitentan on Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension Assessed by Cardiac Magnetic Resonance ImagingPHASE4

COMPLETED · via macitentan · NCT02310672

The Effects of Ambrisentan on Exercise Capacity in Fontan PatientsPHASE4

COMPLETED · via ambrisentan · NCT01971580

Safely Change From Bosentan to Ambrisentan in Pulmonary HypertensionPHASE4

COMPLETED · via ambrisentan · NCT01330108

Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan: A Prospective Single Center, Open Label, Pilot StudyPHASE4

COMPLETED · via ambrisentan · NCT01051960

Safety and Efficacy Trial Using Ambrisentan for Pulmonary Hypertension Associated With Congestive Heart Failure With Preserved Left Ventricular Ejection FractionPHASE4

TERMINATED · via ambrisentan · NCT00840463

An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Patients With Exercise Induced Pulmonary Arterial HypertensionPHASE4

COMPLETED · via ambrisentan · NCT01338636

An Open-label, Multicenter Study of Ambrisentan and a Phosphodiesterase Type-5 Inhibitor Combination Therapy in Subjects With Pulmonary Arterial Hypertension Who Have Demonstrated a Sub-Optimal Response to a Phosphodiesterase Type-5 InhibitorPHASE4

COMPLETED · via ambrisentan · NCT00617305

The Role of MACitentan on the Prevention of Residual Pulmonary vasculaR OcclusionPHASE3

WITHDRAWN · via macitentan · NCT05946811

A Multicenter, Open-label, Phase III Study to Assess the Efficacy, Safety, and Pharmacokinetics of Macitentan in Japanese Pediatric Patients (>=3 Months to <15 Years) With Pulmonary Arterial HypertensionPHASE3

COMPLETED · via macitentan · NCT05167825

Initial Dual Oral coMbination Therapy Versus Standard-of-care Initial Oral Monotherapy Prior to Balloon Pulmonary Angioplasty in Patients With Inoperable Chronic Thromboembolic Pulmonary hyperTensionPHASE2/PHASE3

COMPLETED · via macitentan · NCT04780932

A Prospective, Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel Group, Adaptive Phase 3 Study With Open-label Extension to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary HypertensionPHASE3

TERMINATED · via macitentan · NCT04271475

mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Experimental Drugs and Mechanisms (TACTIC-E)PHASE2/PHASE3

COMPLETED · via ambrisentan · NCT04393246

Prospective, Multi-center, Double-blind, Randomized, Active-controlled, Triple-dummy, Parallel-group, Group-sequential, Adaptive Phase 3 Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed Dose Combination in Subjects With Pulmonary Arterial Hypertension (PAH), Followed by an Open-label Treatment Period With Macitentan and Tadalafil Fixed Dose Combination TherapyPHASE3

COMPLETED · via macitentan · NCT03904693

Prospective, Multi-center, Single-arm, Open-label Long-term Study Assessing the Safety, Tolerability, and Effectiveness of Macitentan in Fontan-palliated Adult and Adolescent SubjectsPHASE3

TERMINATED · via macitentan · NCT03775421

A Prospective, Multicenter, Open-label, Single Arm, Phase III Study to Assess the Efficacy and Safety of Macitentan (ACT-064992) in Subjects With Chronic Thromboembolic Pulmonary Hypertension (CTEPH)PHASE3

TERMINATED · via macitentan · NCT03809650

A Multicenter Open Label Study to Evaluate Efficacy and Safety of China Made Ambrisentan in Chinese Patients With Pulmonary Arterial HypertensionPHASE3

COMPLETED · via ambrisentan · NCT05437224

CompRehensive Phenotypic Characterization of Patients With Scleroderma-Associated Interstitial Lung DiseasE and Pulmonary Hypertension (PH): The CRuSADE PH StudyPHASE2/PHASE3

WITHDRAWN · via macitentan · NCT03726398

mUlticenter, Single-arM, Open-laBel, Long-teRm Safety Study With macitEntan in Patients With puLmonary Arterial Hypertension previousLy Treated With mAcitentan in Clinical StudiesPHASE3

COMPLETED · via macitentan · NCT03422328

ClinicalTrials.gov via the drug-target graph.

What's happening now

9

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 3 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Regulatory approval2026-06-08

    Approval: MACITENTAN (ANDA211000)

    fda · regulatory · fda · via macitentan

  2. Regulatory approval2026-06-08

    Approval: MACITENTAN (ANDA211187)

    fda · regulatory · fda · via macitentan

  3. Regulatory approval2025-09-24

    Approval: Macitentan Accord (EMA)

    ema · regulatory · ema · via macitentan

  4. Regulatory approval2025-09-24

    Approval: Macitentan AccordPharma (EMA)

    ema · regulatory · ema · via macitentan

  5. Regulatory approval2019-06-20

    Approval: Ambrisentan Viatris (previously Ambrisentan Mylan) (EMA)

    ema · regulatory · ema · via ambrisentan

  6. Safety communication2014-12-11

    Drug Safety Update: Sitaxentan (Thelin▼): worldwide withdrawal from the market

    mhra · safety · mhra · via sitaxentan

  7. Regulatory approval2013-12-20

    Approval: Opsumit (EMA)

    ema · regulatory · ema · via macitentan

  8. New publication2012-12-01
    Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study.

    Arthritis and rheumatism · 2012 · 49 citations · Europe PMC · via ambrisentan

  9. Regulatory approval2008-04-21

    Approval: Volibris (EMA)

    ema · regulatory · ema · via ambrisentan

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.