Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTE2YJR)

• DTT Name: Lysophosphatidate-3 receptor (LPAR3)
• Synonyms: Lysophosphatidic acid receptor Edg7; Lysophosphatidic acid receptor 3; LPAR3; LPA3; LPA receptor 3
• Gene Name: LPAR3
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: LPAR3_HUMAN
• TTD ID: T95923
• Sequence:
  MNECHYDKHMDFFYNRSNTDTVDDWTGTKLVIVLCVGTFFCLFIFFSNSLVIAAVIKNRK
  FHFPFYYLLANLAAADFFAGIAYVFLMFNTGPVSKTLTVNRWFLRQGLLDSSLTASLTNL
  LVIAVERHMSIMRMRVHSNLTKKRVTLLILLVWAIAIFMGAVPTLGWNCLCNISACSSLA
  PIYSRSYLVFWTVSNLMAFLIMVVVYLRIYVYVKRKTNVLSPHTSGSISRRRTPMKLMKT
  VMTVLGAFVVCWTPGLVVLLLDGLNCRQCGVQHVKRWFLLLALLNSVVNPIIYSYKDEDM
  YGTMKKMICCFSQENPERRPSRIPSTVLSRSDTGSQYIEDSISQGAVCNKSTS
• Function: Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. May play a role in the development of ovarian cancer. Seems to be coupled to the G(i)/G(o) and G(q) families of heteromeric G proteins.
• KEGG Pathway:
  Rap1 signaling pathway (hsa04015)
  Neuroactive ligand-receptor interaction (hsa04080)
  PI3K-Akt signaling pathway (hsa04151)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Lysosphingolipid and LPA receptors (R-HSA-419408)
  G alpha (q) signalling events (R-HSA-416476)

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
SAR-100842	DMDMQW0	Fibrosis	GA14-GC01	Phase 2	[1]

15 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-oleoyl-LPA	DMN9OS1	Discovery agent	N.A.	Investigative	[2]
alkyl OMPT	DMM19AO	Discovery agent	N.A.	Investigative	[3]
alpha-fluoromethylenephosphonate	DM4GLZU	Discovery agent	N.A.	Investigative	[4]
dioctanoylglycerol pyrophosphate	DM0QY1V	Discovery agent	N.A.	Investigative	[5]
dodecyl-thiophosphate	DMAJVPI	Discovery agent	N.A.	Investigative	[6]
dodecylphosphate	DMPCLTW	Discovery agent	N.A.	Investigative	[7]
Ki16425	DMJTDK9	Discovery agent	N.A.	Investigative	[8]
LPA	DMI5XR1	Discovery agent	N.A.	Investigative	[9]
NAEPA	DM38XWZ	Discovery agent	N.A.	Investigative	[10]
oleoyl-thiophosphate	DM1TAM9	Discovery agent	N.A.	Investigative	[6]
OMPT	DMGFRSY	Discovery agent	N.A.	Investigative	[11]
PMID19800804C12	DMQXK4B	Discovery agent	N.A.	Investigative	[12]
T13	DMVRJEL	Discovery agent	N.A.	Investigative	[10]
VPC12249	DM6F0VR	Discovery agent	N.A.	Investigative	[13]
VPC32183	DMLK3I9	Discovery agent	N.A.	Investigative	[14]

References

• [1] Promising Pharmacological Directions in the World of Lysophosphatidic Acid Signaling. Biomol Ther (Seoul) 2015 January; 23(1): 1-11.
• [2] Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species. Structure-activity relationship of cloned LPA receptors. FEBS Lett. 2000 Jul 28;478(1-2):159-65.
• [3] Phosphorothioate analogues of alkyl lysophosphatidic acid as LPA3 receptor-selective agonists. ChemMedChem. 2006 Mar;1(3):376-83.
• [4] Structure-activity relationships of fluorinated lysophosphatidic acid analogues. J Med Chem. 2005 May 5;48(9):3319-27.
• [5] Short-chain phosphatidates are subtype-selective antagonists of lysophosphatidic acid receptors. Mol Pharmacol. 2001 Oct;60(4):776-84.
• [6] Synthesis, structure-activity relationships, and biological evaluation of fatty alcohol phosphates as lysophosphatidic acid receptor ligands, activ... J Med Chem. 2005 Jul 28;48(15):4919-30.
• [7] Fatty alcohol phosphates are subtype-selective agonists and antagonists of lysophosphatidic acid receptors. Mol Pharmacol. 2003 May;63(5):1032-42.
• [8] Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol Pharmacol. 2003 Oct;64(4):994-1005.
• [9] Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid. J Biol Chem. 1999 Sep 24;274(39):27776-85.
• [10] LPA and its analogs-attractive tools for elucidation of LPA biology and drug development. Curr Med Chem. 2008;15(21):2122-31.
• [11] Identification of a phosphothionate analogue of lysophosphatidic acid (LPA) as a selective agonist of the LPA3 receptor. J Biol Chem. 2003 Apr 4;278(14):11962-9.
• [12] Structure-based drug design identifies novel LPA3 antagonists. Bioorg Med Chem. 2009 Nov 1;17(21):7457-64.
• [13] Activity of 2-substituted lysophosphatidic acid (LPA) analogs at LPA receptors: discovery of a LPA1/LPA3 receptor antagonist. Mol Pharmacol. 2001 Dec;60(6):1173-80.
• [14] Initial structure-activity relationships of lysophosphatidic acid receptor antagonists: discovery of a high-affinity LPA1/LPA3 receptor antagonist. Bioorg Med Chem Lett. 2004 Jun 7;14(11):2735-40.