Target Information
| Target General Information | Top | |||||
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| Target ID |
T95923
(Former ID: TTDI02116)
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| Target Name |
Lysophosphatidate-3 receptor (LPAR3)
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| Synonyms |
Lysophosphatidic acid receptor Edg7; Lysophosphatidic acid receptor 3; LPAR3; LPA3; LPA receptor 3
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| Gene Name |
LPAR3
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Fibrosis [ICD-11: GA14-GC01] | |||||
| 2 | Systemic sclerosis [ICD-11: 4A42] | |||||
| 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.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MNECHYDKHMDFFYNRSNTDTVDDWTGTKLVIVLCVGTFFCLFIFFSNSLVIAAVIKNRK
FHFPFYYLLANLAAADFFAGIAYVFLMFNTGPVSKTLTVNRWFLRQGLLDSSLTASLTNL LVIAVERHMSIMRMRVHSNLTKKRVTLLILLVWAIAIFMGAVPTLGWNCLCNISACSSLA PIYSRSYLVFWTVSNLMAFLIMVVVYLRIYVYVKRKTNVLSPHTSGSISRRRTPMKLMKT VMTVLGAFVVCWTPGLVVLLLDGLNCRQCGVQHVKRWFLLLALLNSVVNPIIYSYKDEDM YGTMKKMICCFSQENPERRPSRIPSTVLSRSDTGSQYIEDSISQGAVCNKSTS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | SAR-100842 | Drug Info | Phase 2 | Fibrosis | [2] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | SAR-100842 | Drug Info | [1] | |||
| Agonist | [+] 5 Agonist drugs | + | ||||
| 1 | 2-oleoyl-LPA | Drug Info | [3] | |||
| 2 | alpha-fluoromethylenephosphonate | Drug Info | [4] | |||
| 3 | NAEPA | Drug Info | [9] | |||
| 4 | oleoyl-thiophosphate | Drug Info | [6] | |||
| 5 | OMPT | Drug Info | [10] | |||
| Antagonist | [+] 7 Antagonist drugs | + | ||||
| 1 | dioctanoylglycerol pyrophosphate | Drug Info | [5] | |||
| 2 | dodecyl-thiophosphate | Drug Info | [6] | |||
| 3 | dodecylphosphate | Drug Info | [7] | |||
| 4 | Ki16425 | Drug Info | [8] | |||
| 5 | PMID19800804C12 | Drug Info | [11] | |||
| 6 | VPC12249 | Drug Info | [12] | |||
| 7 | VPC32183 | Drug Info | [13] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Rap1 signaling pathway | hsa04015 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Phospholipase D signaling pathway | hsa04072 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 1.39E-04 |
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| Closeness centrality | 1.86E-01 | Radiality | 1.31E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.53E+01 | Topological coefficient | 2.74E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Rap1 signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| 3 | PI3K-Akt signaling pathway | |||||
| 4 | Pathways in cancer | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | LPA receptor mediated events | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | G alpha (q) signalling events | |||||
| 2 | G alpha (i) signalling events | |||||
| 3 | Lysosphingolipid and LPA receptors | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 2 | GPCR ligand binding | |||||
| 3 | GPCR downstream signaling | |||||
| References | Top | |||||
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| REF 1 | Promising Pharmacological Directions in the World of Lysophosphatidic Acid Signaling. Biomol Ther (Seoul) 2015 January; 23(1): 1-11. | |||||
| REF 2 | ClinicalTrials.gov (NCT01651143) Proof of Biological Activity of SAR100842 in Systemic Sclerosis. U.S. National Institutes of Health. | |||||
| REF 3 | 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. | |||||
| REF 4 | Structure-activity relationships of fluorinated lysophosphatidic acid analogues. J Med Chem. 2005 May 5;48(9):3319-27. | |||||
| REF 5 | Short-chain phosphatidates are subtype-selective antagonists of lysophosphatidic acid receptors. Mol Pharmacol. 2001 Oct;60(4):776-84. | |||||
| REF 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. | |||||
| REF 7 | Fatty alcohol phosphates are subtype-selective agonists and antagonists of lysophosphatidic acid receptors. Mol Pharmacol. 2003 May;63(5):1032-42. | |||||
| REF 8 | Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol Pharmacol. 2003 Oct;64(4):994-1005. | |||||
| REF 9 | LPA and its analogs-attractive tools for elucidation of LPA biology and drug development. Curr Med Chem. 2008;15(21):2122-31. | |||||
| REF 10 | 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. | |||||
| REF 11 | Structure-based drug design identifies novel LPA3 antagonists. Bioorg Med Chem. 2009 Nov 1;17(21):7457-64. | |||||
| REF 12 | 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. | |||||
| REF 13 | 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. | |||||
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