Protein / target

Apelin receptor

APLNRP35414Homo sapiensSwiss-Prot
Clinical-stage
Therapeutic maturity
1
Clinical candidates
9
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

G protein-coupled peptide receptor activity

Primary system

Cardiovascular system

Strongest disease association

essential hypertension

Genetic evidence · score 0.28

Therapeutic maturity

Clinical-stage target

1 candidate in clinical development

Druggability

Small molecule

Open Targets tractability · Structure with Ligand

Clinical development

1 in clinical development

9 linked trials

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

G protein-coupled receptor for peptide hormones apelin (APLN) and apelin receptor early endogenous ligand (APELA/ELA), that plays a role in the regulation of normal cardiovascular function and fluid homeostasis (PubMed:11090199, PubMed:22810587, PubMed:25639753, PubMed:28137936, PubMed:35817871, PubMed:38428423). When acting as apelin receptor, activates both G(i) protein pathway that inhibits adenylate cyclase activity, and the beta-arrestin pathway that promotes internalization of the receptor (PubMed:11090199, PubMed:25639753, PubMed:28137936, PubMed:35817871, PubMed:38428423). APLNR/APJ also functions as mechanoreceptor that is activated by pathological stimuli in a G protein-independent fashion to induce beta-arrestin signaling, hence eliciting cardiac hypertrophy (PubMed:22810587, PubMed:38428423). However, the presence of apelin ligand blunts cardiac hypertrophic induction from APLNR/APJ on response to pathological stimuli (PubMed:22810587, PubMed:38428423). Plays a key role in early development such as gastrulation, blood vessels formation and heart morphogenesis by acting as a APELA receptor (By similarity). May promote angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis (By similarity). Promotes sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel development (By similarity). Also plays a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility and heart failure (PubMed:25639753, PubMed:28137936)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (34)

Gene Ontology

  • Cplasma membrane
  • Fapelin receptor activity
  • FG protein-coupled peptide receptor activity
  • FG protein-coupled receptor activity
  • Fmechanoreceptor activity
  • Fsignaling receptor activity
  • Padenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
  • Padult heart development
  • Pangiogenesis
  • Paorta development
  • Papelin receptor signaling pathway
  • Patrioventricular valve development

380 aa · 43 kDa

Biological roles

Reactome v97

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

G protein-coupled signallingUniProt · GOTranscriptional regulationGO
View supporting evidence

G protein-coupled signalling

  • ·G protein-coupled receptor for peptide hormones apelin (APLN) and apelin receptor early…
  • ·G protein-coupled peptide receptor activity
  • ·G protein-coupled receptor activity
  • ·adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway

Transcriptional regulation

  • ·negative regulation of gene expression
  • ·regulation of gene expression
View underlying pathways (2)

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

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

APLNAPELAGNB4GNB1GNB3GNB2GNB5GNAQGNA13GNGT1APLNR

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Apelin
Narrow target profilePhase 2Agonist

Apelin receptor agonist

Appears in clinical studies involving type 2 diabetes mellitus, heart failure, pulmonary hypertension, pulmonary arterial hypertension

Direct interaction with this protein · Only this protein recorded as a target

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

essential hypertension0.28

Genetic · overall 0.17

hypertensive disorder0.16

Genetic · overall 0.12

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

type 2 diabetes mellitus0.14

Clinical · overall 0.09

pulmonary arterial hypertension0.01

Clinical · overall 0.10

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

neoplasm0.11

Literature

glioblastoma0.08

Literature

cancer0.08

Literature

metabolic dysfunction-associated steatotic liver disease0.08

Literature

coronary artery disorder0.07

Literature

Show all associations
essential hypertension0.17
hypertensive disorder0.12
neoplasm0.11
pulmonary arterial hypertension0.10
type 2 diabetes mellitus0.09
glioblastoma0.08
cancer0.08
metabolic dysfunction-associated steatotic liver disease0.08
coronary artery disorder0.07
hepatocellular carcinoma0.07

Open Targets ranks 458 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 1 total

APELINPhase 2

type 2 diabetes mellitus · heart failure · pulmonary hypertension

Tractability

SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule BinderOC · Advanced Clinical

Clinical trials

9

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

pulmonary arterial hypertensionLimited support
0.30
agreement 0.170.42
Animal model65%Literature34%Clinical1%

Open Targets aggregate 0.10 · 3 independent evidence families

essential hypertensionLimited support
0.29
agreement 0.160.43
Genetic93%Literature7%

Open Targets aggregate 0.17 · 2 independent evidence families

hypertensive disorderPreliminary
0.23
agreement 0.100.37
Genetic65%Literature35%

Open Targets aggregate 0.12 · 2 independent evidence families

neoplasmPreliminary
0.13
agreement 0.000.41
Literature100%

Open Targets aggregate 0.11 · 1 independent evidence family · no direct causal or clinical evidence

type 2 diabetes mellitusPreliminary
0.12
agreement 0.000.28
Clinical82%Literature18%

Open Targets aggregate 0.09 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

3

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2024-08-09
    Impact of Smoking and Obesity on the Selected Peptide Hormones and Metabolic Parameters in the Blood of Women with Polycystic Ovary Syndrome-Preliminary Study.

    International journal of molecular sciences · 2024 · 5 citations · Europe PMC · via Apelin

  2. New publication2023-12-01
    Targeting the apelin system for the treatment of cardiovascular diseases.

    Cardiovascular research · 2023 · 59 citations · Europe PMC · via Apelin

  3. New publication2023-11-28
    Beneficial effects of Apelin-13 on metabolic diseases and exercise.

    Frontiers in endocrinology · 2023 · 12 citations · Europe PMC · via Apelin

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.