Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJ8E43)

• DTT Name: Apelin receptor (APLNR)
• Synonyms: G-protein coupled receptor HG11; G-protein coupled receptor APJ; Angiotensin receptor-like 1; APJ; AGTRL1
• Gene Name: APLNR
• DTT Type: Clinical trial target; [1]
• UniProt ID: APJ_HUMAN
• TTD ID: T65783
• Sequence:
  MEEGGDFDNYYGADNQSECEYTDWKSSGALIPAIYMLVFLLGTTGNGLVLWTVFRSSREK
  RRSADIFIASLAVADLTFVVTLPLWATYTYRDYDWPFGTFFCKLSSYLIFVNMYASVFCL
  TGLSFDRYLAIVRPVANARLRLRVSGAVATAVLWVLAALLAMPVMVLRTTGDLENTTKVQ
  CYMDYSMVATVSSEWAWEVGLGVSSTTVGFVVPFTIMLTCYFFIAQTIAGHFRKERIEGL
  RKRRRLLSIIVVLVVTFALCWMPYHLVKTLYMLGSLLHWPCDFDLFLMNIFPYCTCISYV
  NSCLNPFLYAFFDPRFRQACTSMLCCGQSRCAGTSHSSSGEKSASYSSGHSQGPGPNMGK
  GGEQMHEKSIPYSQETLVVD
• Function: Receptor for apelin receptor early endogenous ligand (APELA) and apelin (APLN) hormones coupled to G proteins that inhibit adenylate cyclase activity. Plays a key role in early development such as gastrulation, blood vessels formation and heart morphogenesis by acting as a receptor for APELA hormone (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). Plays also a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility and heart failure.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Apelin signaling pathway (hsa04371)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AMG 986	DMZQ2DK	Heart failure	BD10-BD13	Phase 1	[1]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
apelin-13	DM2CKUZ	Discovery agent	N.A.	Investigative	[2]
E339-3D6	DMGPRT7	Discovery agent	N.A.	Investigative	[3]
ML221	DM3OEP4	Discovery agent	N.A.	Investigative	[4]
ML233	DM8CIE4	Discovery agent	N.A.	Investigative	[5]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Structural and functional study of the apelin-13 peptide, an endogenous ligand of the HIV-1 coreceptor, APJ. Biochemistry. 2003 Sep 2;42(34):10163-8.
• [3] Identification and pharmacological properties of E339-3D6, the first nonpeptidic apelin receptor agonist. FASEB J. 2010 May;24(5):1506-17.
• [4] Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor. Bioorg Med Chem Lett. 2012 Nov 1;22(21):6656-60.
• [5] Functional Agonists of the Apelin (APJ) Receptor. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010.