LPAR1

Summary

LPAR1 (lysophosphatidic acid receptor 1, HGNC:3166) is a protein-coding gene on chromosome 9q31.3, encoding Lysophosphatidic acid receptor 1 (Q92633). Receptor for lysophosphatidic acid (LPA).

The integral membrane protein encoded by this gene is a lysophosphatidic acid (LPA) receptor from a group known as EDG receptors. These receptors are members of the G protein-coupled receptor superfamily. Utilized by LPA for cell signaling, EDG receptors mediate diverse biologic functions, including proliferation, platelet aggregation, smooth muscle contraction, inhibition of neuroblastoma cell differentiation, chemotaxis, and tumor cell invasion. Many transcript variants encoding a few different isoforms have been identified for this gene.

Source: NCBI Gene 1902 — RefSeq curated summary.

At a glance

• GWAS associations: 36
• Clinical variants (ClinVar): 49 total — 1 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001351411

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3166
Approved symbol	LPAR1
Name	lysophosphatidic acid receptor 1
Location	9q31.3
Locus type	gene with protein product
Status	Approved
Aliases	edg-2, rec.1.3, vzg-1, Gpcr26, Mrec1.3, LPA1
Ensembl gene	ENSG00000198121
Ensembl biotype	protein_coding
OMIM	602282
Entrez	1902

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 44 protein_coding

ENST00000358883, ENST00000374430, ENST00000374431, ENST00000441240, ENST00000683809, ENST00000853434, ENST00000853435, ENST00000853436, ENST00000853437, ENST00000853438, ENST00000853439, ENST00000853440, ENST00000853441, ENST00000853442, ENST00000853443, ENST00000853444, ENST00000853445, ENST00000853446, ENST00000853447, ENST00000853448, ENST00000853449, ENST00000853450, ENST00000853451, ENST00000853452, ENST00000853453, ENST00000853454, ENST00000853455, ENST00000853456, ENST00000853457, ENST00000853458, ENST00000853459, ENST00000937390, ENST00000965564, ENST00000965565, ENST00000965566, ENST00000965567, ENST00000965568, ENST00000965569, ENST00000965570, ENST00000965571, ENST00000965572, ENST00000965573, ENST00000965574, ENST00000965575

RefSeq mRNA: 76 — MANE Select: NM_001351411 NM_001351397, NM_001351398, NM_001351399, NM_001351400, NM_001351401, NM_001351402, NM_001351403, NM_001351404, NM_001351405, NM_001351406, NM_001351407, NM_001351408, NM_001351409, NM_001351410, NM_001351411, NM_001351412, NM_001351413, NM_001351414, NM_001351415, NM_001351416, NM_001351417, NM_001351418, NM_001351419, NM_001351420, NM_001387470, NM_001387471, NM_001387472, NM_001387473, NM_001387474, NM_001387475, NM_001387476, NM_001387477, NM_001387478, NM_001387479, NM_001387480, NM_001387481, NM_001387482, NM_001387483, NM_001387484, NM_001387485, NM_001387486, NM_001387487, NM_001387488, NM_001387489, NM_001387490, NM_001387491, NM_001387492, NM_001387493, NM_001387494, NM_001387495, NM_001387496, NM_001387497, NM_001387498, NM_001387501, NM_001387502, NM_001387503, NM_001387504, NM_001387505, NM_001387506, NM_001387507, NM_001387508, NM_001387509, NM_001387510, NM_001387511, NM_001387512, NM_001387513, NM_001387514, NM_001387515, NM_001387516, NM_001387517, NM_001387518, NM_001387519, NM_001387520, NM_001387521, NM_001401, NM_057159

CCDS: CCDS6777

Canonical transcript exons

ENST00000683809 — 6 exons

Exon	Start	End
ENSE00001221308	110973481	110973558
ENSE00001920496	110873263	110875722
ENSE00002724435	110972073	110972220
ENSE00003716004	110941421	110942168
ENSE00003919149	111036122	111036201
ENSE00003921943	111038167	111038470

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.9715 / max 647.7846, expressed in 1323 samples.

FANTOM5 promoters (32 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101968	15.3064	1188
101966	3.5912	821
101972	2.5601	823
101964	1.6747	793
101974	0.9013	563
101965	0.7146	465
101948	0.7038	72
101973	0.5002	326
101960	0.4749	246
101975	0.4593	338

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	99.77	gold quality
tendon of biceps brachii	UBERON:0008188	99.72	gold quality
globus pallidus	UBERON:0001875	99.67	gold quality
inferior vagus X ganglion	UBERON:0005363	99.18	gold quality
lateral globus pallidus	UBERON:0002476	99.06	gold quality
cranial nerve II	UBERON:0000941	98.94	gold quality
corpus callosum	UBERON:0002336	98.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.91	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.90	gold quality
subthalamic nucleus	UBERON:0001906	98.76	gold quality
inferior olivary complex	UBERON:0002127	98.62	gold quality
spinal cord	UBERON:0002240	98.51	gold quality
medulla oblongata	UBERON:0001896	98.38	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.19	gold quality
substantia nigra	UBERON:0002038	98.13	gold quality
midbrain	UBERON:0001891	98.09	gold quality
endothelial cell	CL:0000115	98.08	gold quality
superior vestibular nucleus	UBERON:0007227	97.88	gold quality
putamen	UBERON:0001874	97.87	gold quality
amygdala	UBERON:0001876	97.62	gold quality
ventral tegmental area	UBERON:0002691	97.51	gold quality
tendon	UBERON:0000043	97.49	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.25	gold quality
substantia nigra pars compacta	UBERON:0001965	97.22	gold quality
cartilage tissue	UBERON:0002418	97.22	gold quality
stromal cell of endometrium	CL:0002255	97.03	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.02	gold quality
Ammon’s horn	UBERON:0001954	96.94	gold quality
trigeminal ganglion	UBERON:0001675	96.76	gold quality
olfactory bulb	UBERON:0002264	96.73	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	76.71
E-ANND-3	yes	27.71
E-MTAB-9388	yes	10.92
E-GEOD-84465	yes	9.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NME1, PBX4

miRNA regulators (miRDB)

154 targeting LPAR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8063	99.91	69.76	3146

Literature-anchored findings (GeneRIF, showing 40)

• LP(A1) and myelin basic protein colocalized in brain, but oligodendrocyte soma showed stronger signals for LP(A1) than myelinated fibers, whereas the reverse was true for myelin basic protein so LP(A1) may be involved in myelin formation or maintenance. (PMID:11948806)
• demonstrate that two biological fluids, blood plasma and seminal plasma, differentially activate LPA receptors (PMID:12123830)
• Data suggest that LPA(1) receptors couple to a G(i)-phosphoinositide 3-kinase-Tiam1 pathway to activate Rac, with consequent suppression of RhoA activity, and thereby stimulate cell spreading and motility. (PMID:12393875)
• lysophosphatidic acid-coupled LPA1/EDG-2 receptors are endocytosed via a dynamin2- and Rab5-dependent pathway (PMID:12668728)
• LPA acts as a potent stimulator of colon cancer progression, although the binding to LPA1 and LPA2 induces slightly different responses. (PMID:12670925)
• LPA stimulation promotes the interaction of the LPA(2) receptor with a focal adhesion molecule, TRIP6 (PMID:14688263)
• EDG-2 expression was increased in low-grade adenoma compared with that in normal mucosa (P < 0.001). EDG-2 expression was significantly greater in adenomas with larger diameters (P < 0.001). (PMID:14696401)
• Amyloid beta-protein stimulated in monocytes the gene expression for sphingosine-1-phosphate receptor 2, which is amyloid beta-protein-induced migration. (PMID:15208267)
• data suggest that endothelial differentiation gene EDG-7 and EDG-2 lysophosphatidic acid receptors play a diverse role in mesangial cell proliferation (PMID:15292052)
• formation of the LPA receptor/PDZ domain-containing RhoGEF complex plays a pivotal role in LPA-induced RhoA activation (PMID:15755723)
• We show that in addition to promoting LPA(1) signaling, membrane cholesterol is essential for the association of LPA(1) with beta-arrestin, which leads to signal attenuation and clathrin-dependent endocytosis of LPA(1). (PMID:16263766)
• These findings demonstrate that trafficking of LPA1 to the nucleus is influenced by cell-matrix interactions and that nuclear LPA1 may be involved in regulating intranuclear protein phosphorylation and signalling. (PMID:16716145)
• LPA(1) transduces Galphai-dependent signals to promote nuclear localization of androgen receptor and cell proliferation (PMID:16809448)
• EDG2 and EDG4 cooperate to promote LPA-stimulated chemotaxis in breast tumor cell lines. (PMID:17496233)
• The results of the present study suggest that lysophosphatidic acid (LPA), the receptor LPA(1), ERK2 and p38alpha are important regulators for prostate cancer cell invasion and thus could play a significant role in the development of metastasis. (PMID:17531530)
• expression of LPA-induced inflammatory response genes is mediated by LPA1 and LPA3 (PMID:17923111)
• Lysophosphatidic acid receptor 1 may contribute to the pathogenesis of rheumatoid arthritis through the modulation of fibroblast-like synoviocyte migration and cytokine production. (PMID:18006645)
• distinct molecular mechanisms regulate agonist-dependent and PMA-dependent internalization of the LPA 1 receptor. (PMID:18089565)
• Down-regulation of EDG2 is functionally important to suppression of tumor metastasis in breast neoplasms. (PMID:18089805)
• Through the stepwise association study, an SNP located in the promoter region of EDG2 (-2,820G/A; rs10980705) showed significant association with knee osteoarthritis in two independent populations. (PMID:18325907)
• LPA may play a role in angiogenesis of endometrium and placenta through induction of IL-8 in endometrial stromal cells during pregnancy. (PMID:18617617)
• The original report of a promising genetic association between a druggable G-protein coupled receptor, EDG2, and knee OA has not been replicated. (PMID:18625619)
• Lysophosphatidic acid might regulate VEGF-C and lymphatic marker expression in endothelial cells, which contributes to endothelial cell tube formation in vitro and in vivo, thus facilitating endothelial cell participation lymphangiogenesis. (PMID:18627789)
• A role for the transgenic lysophosphatidic acid (LPA)1 receptor is identified in regulating smooth muscle cell migratory responses in the context of vascular injury. (PMID:18703779)
• These results indicate that LPA is a critical factor on proliferation though LPA(1), and on motility though LPA(2) in MPM cells. (PMID:18754873)
• Switching of LPA receptor expression from LPA3 to LPA1, may be involved in prostate cancer progression and/or androgen independence (PMID:19025891)
• LPA(1) receptor, LPA(2) and LPA(3) receptors-induced VASP phosphorylation is a critical mediator of tumor cell migration initiation (PMID:19081821)
• These results establish RalA and GRK2 as key regulators of LPA receptor signalling and demonstrate for the first time that LPA(1) activity facilitates the formation of a novel protein complex between these two proteins. (PMID:19306925)
• LPA-stimulated cell growth is mediated by distinct but overlapping receptors and signaling pathways in these two model ovarian cancer cell lines. (PMID:19420982)
• Data show that CLL cells express LPA receptors LPA(1-5) and VEGF receptors, and the plasma levels of VEGF are elevated in CLL patients. (PMID:19860625)
• show that human microglia express LPA receptor subtypes LPA(1), LPA(2), and LPA(3) on mRNA and protein level. LPA activation of C13NJ cells induced Rho and extracellular signal-regulated kinase activation and enhanced cellular ATP production. (PMID:19899077)
• LPA1 receptor has a role in angiogenesis in tumor cells and xenografts (PMID:20708100)
• Mutation in LPA1 gene indicate that alteration in LPA receptor gene may play some role in the pathogenesis in human osteosarcoma cells. (PMID:21116120)
• This work shows for the first time that key components of the LPA pathway are modulated following traumatic brain injuries in humans. (PMID:21234797)
• the ATX-LPA-LPAR axis is a critical regulator of embryonic vascular development that is conserved in vertebrates (PMID:21971049)
• CD97 functioned to mediate invasion in prostate cancer cells, by associating with lysophosphatidic acid receptor 1 (LPAR1), leading to enhanced LPA-dependent RHO and extracellular signal-regulated kinase activation. (PMID:21978933)
• The ability of LPA-LPA(1) signaling to promote epithelial cell apoptosis and fibroblast resistance to apoptosis may therefore contribute to the capacity of this signaling pathway to regulate the development of pulmonary fibrosis after lung injury. (PMID:22021336)
• a crosslink between Egr-1 and periostin in cancer cells (PMID:22659570)
• CD97 expression in human thyroid cancers correlated with LPA receptor and markers of aggressiveness including Ki67 and pAKT. (PMID:22797060)
• study identified a novel role of TGFbeta in the control of LPA1 expression and LPA1-coupled biological functions, adding LPA1 to the list of TGFbeta-repressed target genes (PMID:22824789)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lpar1	ENSDARG00000099840
mus_musculus	Lpar1	ENSMUSG00000038668
rattus_norvegicus	Lpar1	ENSRNOG00000013656

Paralogs (18): LPAR2 (ENSG00000064547), CNR1 (ENSG00000118432), MC3R (ENSG00000124089), S1PR4 (ENSG00000125910), GPR12 (ENSG00000132975), GPR6 (ENSG00000146360), GPR119 (ENSG00000147262), MC4R (ENSG00000166603), S1PR1 (ENSG00000170989), LPAR3 (ENSG00000171517), MC5R (ENSG00000176136), S1PR5 (ENSG00000180739), GPR3 (ENSG00000181773), MC2R (ENSG00000185231), CNR2 (ENSG00000188822), S1PR3 (ENSG00000213694), MC1R (ENSG00000258839), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

Lysophosphatidic acid receptor 1 — Q92633 (reviewed: Q92633)

Alternative names: Lysophosphatidic acid receptor Edg-2

All UniProt accessions (3): B1AP63, Q92633, Q5VZX0

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for lysophosphatidic acid (LPA). Plays a role in the reorganization of the actin cytoskeleton, cell migration, differentiation and proliferation, and thereby contributes to the responses to tissue damage and infectious agents. Activates downstream signaling cascades via the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Signaling inhibits adenylyl cyclase activity and decreases cellular cAMP levels. Signaling triggers an increase of cytoplasmic Ca(2+) levels. Activates RALA; this leads to the activation of phospholipase C (PLC) and the formation of inositol 1,4,5-trisphosphate. Signaling mediates activation of down-stream MAP kinases. Contributes to the regulation of cell shape. Promotes Rho-dependent reorganization of the actin cytoskeleton in neuronal cells and neurite retraction. Promotes the activation of Rho and the formation of actin stress fibers. Promotes formation of lamellipodia at the leading edge of migrating cells via activation of RAC1. Through its function as LPA receptor, plays a role in chemotaxis and cell migration, including responses to injury and wounding. Plays a role in triggering inflammation in response to bacterial lipopolysaccharide (LPS) via its interaction with CD14. Promotes cell proliferation in response to LPA. Inhibits the intracellular ciliogenesis pathway in response to LPA and through AKT1 activation. Required for normal skeleton development. May play a role in osteoblast differentiation. Required for normal brain development. Required for normal proliferation, survival and maturation of newly formed neurons in the adult dentate gyrus. Plays a role in pain perception and in the initiation of neuropathic pain.

Subunit / interactions. Interacts with RALA and GRK2. Interacts with GNAQ and GNA13. Interacts with CD14; the interaction is enhanced by exposure to bacterial lipopolysaccharide (LPS).

Subcellular location. Cell surface. Cell membrane. Endosome.

Tissue specificity. Expressed in many adult organs, including brain, heart, colon, small intestine, placenta, prostate, ovary, pancreas, testes, spleen, skeletal muscle, and kidney. Little or no expression in liver, lung, thymus, or peripheral blood leukocytes. Detected in lung fibroblasts from bronchoalveolar fluid from patients with idiopathic pulmonary fibrosis. Detected in bone marrow-derived mesenchymal stem cells.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the G-protein coupled receptor 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92633-1	1	yes
Q92633-2	2

RefSeq proteins (76): NP_001338326, NP_001338327, NP_001338328, NP_001338329, NP_001338330, NP_001338331, NP_001338332, NP_001338333, NP_001338334, NP_001338335, NP_001338336, NP_001338337, NP_001338338, NP_001338339, NP_001338340, NP_001338341, NP_001338342, NP_001338343, NP_001338344, NP_001338345, NP_001338346, NP_001338347, NP_001338348, NP_001338349, NP_001374399, NP_001374400, NP_001374401, NP_001374402, NP_001374403, NP_001374404, NP_001374405, NP_001374406, NP_001374407, NP_001374408, NP_001374409, NP_001374410, NP_001374411, NP_001374412, NP_001374413, NP_001374414, NP_001374415, NP_001374416, NP_001374417, NP_001374418, NP_001374419, NP_001374420, NP_001374421, NP_001374422, NP_001374423, NP_001374424, NP_001374425, NP_001374426, NP_001374427, NP_001374430, NP_001374431, NP_001374432, NP_001374433, NP_001374434, NP_001374435, NP_001374436, NP_001374437, NP_001374438, NP_001374439, NP_001374440, NP_001374441, NP_001374442, NP_001374443, NP_001374444, NP_001374445, NP_001374446, NP_001374447, NP_001374448, NP_001374449, NP_001374450, NP_001392, NP_476500 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR002277	LPA_rcpt_EDG2	Family
IPR004065	LPA_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (53 total): helix 12, topological domain 8, transmembrane region 7, strand 7, binding site 3, disulfide bond 3, mutagenesis site 3, modified residue 2, glycosylation site 2, turn 2, chain 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
7TD0	ELECTRON MICROSCOPY	2.83
9J5V	ELECTRON MICROSCOPY	2.86
4Z35	X-RAY DIFFRACTION	2.9
4Z36	X-RAY DIFFRACTION	2.9
4Z34	X-RAY DIFFRACTION	3
9IZG	ELECTRON MICROSCOPY	3.04
9IZH	ELECTRON MICROSCOPY	3.04
7TD1	ELECTRON MICROSCOPY	3.08
7TD2	ELECTRON MICROSCOPY	3.11
9IZF	ELECTRON MICROSCOPY	3.14
7YU3	ELECTRON MICROSCOPY	3.5
7YU4	ELECTRON MICROSCOPY	3.7
7YU5	ELECTRON MICROSCOPY	3.7
7YU6	ELECTRON MICROSCOPY	3.9
7YU7	ELECTRON MICROSCOPY	4.5
7YU8	ELECTRON MICROSCOPY	5.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92633-F1	84.08	0.64

Antibody-complex structures (SAbDab): 6 — 7YU3, 7YU5, 7YU6, 7YU7, 7YU8, 9IZH

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 39; 124–129; 210

Post-translational modifications (2): 341, 351

Disulfide bonds (3): 24–190, 188–195, 284–287

Glycosylation sites (2): 27, 35

Mutagenesis-validated functional residues (3):

Position	Phenotype
85	impairs localization at the cell membrane.
87	impairs localization at the cell membrane.
325–326	impairs localization at the cell membrane.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-419408	Lysosphingolipid and LPA receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 370 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_CELL_CHEMOTAXIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, MODULE_64, AREB6_03, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (33): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), regulation of cell shape (GO:0008360), negative regulation of neuron projection development (GO:0010977), oligodendrocyte development (GO:0014003), cerebellum development (GO:0021549), optic nerve development (GO:0021554), neurogenesis (GO:0022008), corpus callosum development (GO:0022038), bleb assembly (GO:0032060), positive regulation of Rho protein signal transduction (GO:0035025), myelination (GO:0042552), positive regulation of apoptotic process (GO:0043065), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of MAPK cascade (GO:0043410), positive regulation of stress fiber assembly (GO:0051496), cell chemotaxis (GO:0060326), positive regulation of dendritic spine development (GO:0060999), cellular response to oxygen levels (GO:0071453), positive regulation of smooth muscle cell chemotaxis (GO:0071673), regulation of synaptic vesicle cycle (GO:0098693), regulation of postsynaptic neurotransmitter receptor internalization (GO:0099149), negative regulation of cAMP/PKA signal transduction (GO:0141162), negative regulation of cilium assembly (GO:1902018), cellular response to 1-oleoyl-sn-glycerol 3-phosphate (GO:1904566), signal transduction (GO:0007165), Golgi to plasma membrane protein transport (GO:0043001), positive regulation of cilium assembly (GO:0045724), regulation of vesicle-mediated transport (GO:0060627), protein localization to cilium (GO:0061512)

GO Molecular Function (8): G-protein alpha-subunit binding (GO:0001965), G protein-coupled receptor activity (GO:0004930), PDZ domain binding (GO:0030165), lysophosphatidic acid binding (GO:0035727), lysophosphatidic acid receptor activity (GO:0070915), protein binding (GO:0005515), phospholipid binding (GO:0005543), lipid binding (GO:0008289)

GO Cellular Component (13): cytoplasm (GO:0005737), endosome (GO:0005768), plasma membrane (GO:0005886), cell surface (GO:0009986), presynaptic membrane (GO:0042734), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), dendritic shaft (GO:0043198), postsynaptic membrane (GO:0045211), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), membrane (GO:0016020), endocytic vesicle (GO:0030139)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
GPCR downstream signalling	2
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
G protein-coupled receptor signaling pathway	2
regulation of biological quality	2
anatomical structure development	2
positive regulation of intracellular signal transduction	2
binding	2
cytoplasmic vesicle	2
synaptic membrane	2
dendrite	2
postsynapse	2
synapse	2
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase activator activity	1
adenylate cyclase inhibitor activity	1
phospholipase C activator activity	1
regulation of cell morphogenesis	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
glial cell development	1
oligodendrocyte differentiation	1
metencephalon development	1
cranial nerve development	1
nervous system development	1
cell differentiation	1
telencephalon development	1
plasma membrane bounded cell projection assembly	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
axon ensheathment	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
MAPK cascade	1
regulation of MAPK cascade	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

159 interactions, top by confidence:

A	B	Type	Score
FLNA	LPAR1	psi-mi:“MI:2364”(proximity)	0.580
LPAR1	FLNA	psi-mi:“MI:2364”(proximity)	0.580
FLNA	LPAR1	psi-mi:“MI:0914”(association)	0.580
LPAR1	FLNA	psi-mi:“MI:0914”(association)	0.580
FLNA	LPAR1	psi-mi:“MI:0915”(physical association)	0.580
MRTFA	FLNA	psi-mi:“MI:0914”(association)	0.570
GAMT	FARS2	psi-mi:“MI:0914”(association)	0.560
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
MRTFA	LPAR1	psi-mi:“MI:2364”(proximity)	0.500
LPAR1	MRTFA	psi-mi:“MI:2364”(proximity)	0.500
LPAR1	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
LPAR1	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
LPAR1	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
LPAR1	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
LPAR1	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
LPAR1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
LPAR1	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
LPAR1	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
LPAR1	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (340): LPAR1 (Affinity Capture-Western), ITGB4 (Affinity Capture-Western), ENPP2 (Affinity Capture-Western), LPAR1 (Affinity Capture-MS), MBOAT7 (Affinity Capture-MS), GOLGA5 (Affinity Capture-MS), TYRO3 (Affinity Capture-MS), PIGO (Affinity Capture-MS), SLC9A1 (Affinity Capture-MS), GOLGB1 (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), GPRC5C (Affinity Capture-MS), SCAP (Affinity Capture-MS), KTN1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS)

ESM2 similar proteins: A6NMU1, B3DH96, O01608, O13076, O17819, O17820, O97504, P32244, P32245, P33032, P34974, P35345, P37289, P41149, P41968, P43118, P52592, P54127, P61793, P61794, P70115, Q01718, Q0Z8I9, Q28031, Q28905, Q5QD16, Q5QD17, Q5QD24, Q5QD25, Q5QD29, Q5QNP2, Q64326, Q6W049, Q8HXX3, Q8HYN8, Q8HZ64, Q8K5E0, Q923Y7, Q92633, Q96RJ0

Diamond homologs: E7EM37, O02213, O02777, O08530, O42384, O73810, O95136, O95977, P14416, P18089, P19020, P19328, P20272, P20288, P21453, P21554, P22270, P24628, P28286, P30545, P30728, P30951, P34972, P34973, P35412, P35462, P46089, P46095, P46628, P47746, P47752, P47936, P48303, P51651, P52592, P52702, P52703, P53453, P56971, P60026

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
“lysophosphatidic acids”	up-regulates	LPAR1	“chemical activation”
LPAR1	up-regulates	GNA12	binding
LPAR1	up-regulates	GNAQ	binding
“3-[({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-1,2-oxazol-5-yl]phenyl}methyl)sulfanyl]propanoic acid”	down-regulates	LPAR1	“chemical inhibition”
LPAR1	up-regulates	GNA13	binding
NME1	“down-regulates quantity by repression”	LPAR1	“transcriptional regulation”
LPAR1	“up-regulates activity”	GNAI1	binding
LPAR1	“up-regulates activity”	GNAI3	binding
LPAR1	“up-regulates activity”	GNAO1	binding
LPAR1	“up-regulates activity”	GNAQ	binding
LPAR1	“up-regulates activity”	GNA14	binding
LPAR1	“up-regulates activity”	GNA15	binding
LPAR1	“up-regulates activity”	GNA12	binding
LPAR1	“up-regulates activity”	GNA13	binding
“lysophosphatidic acid”	“up-regulates activity”	LPAR1	“chemical activation”
LPAR1	up-regulates	GNAI1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	6	51.9×	1e-07
Unblocking of NMDA receptors, glutamate binding and activation	5	41.2×	7e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	41.2×	7e-06
Long-term potentiation	5	36.0×	1e-05
Assembly and cell surface presentation of NMDA receptors	9	34.6×	5e-10
Neurexins and neuroligins	10	29.8×	3e-10
Protein-protein interactions at synapses	6	24.1×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	68.0×	2e-15
receptor clustering	8	53.1×	5e-10
protein localization to synapse	6	48.9×	3e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	36.9×	2e-07
bicellular tight junction assembly	5	17.6×	5e-04
cell-cell adhesion	11	11.9×	3e-07
protein-containing complex assembly	9	10.9×	1e-05
protein localization to plasma membrane	9	10.4×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

49 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	39
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
563672	GRCh37/hg19 9q31.2-32(chr9:108664157-115356416)x3	Likely pathogenic

SpliceAI

1985 predictions. Top by Δscore:

Variant	Effect	Δscore
9:110941414:AACTT:A	donor_loss	1.0000
9:110941415:ACTT:A	donor_loss	1.0000
9:110941416:CTT:C	donor_loss	1.0000
9:110941417:TTACC:T	donor_loss	1.0000
9:110941418:TACC:T	donor_loss	1.0000
9:110941419:A:AC	donor_gain	1.0000
9:110941420:C:CC	donor_gain	1.0000
9:110941420:C:CG	donor_loss	1.0000
9:110941420:CCAAG:C	donor_gain	1.0000
9:110942164:GTGAA:G	acceptor_gain	1.0000
9:110942165:TGAA:T	acceptor_gain	1.0000
9:110942166:GAA:G	acceptor_gain	1.0000
9:110942167:AA:A	acceptor_gain	1.0000
9:110942169:C:CC	acceptor_gain	1.0000
9:110972067:CCTTA:C	donor_loss	1.0000
9:110972068:CTTAC:C	donor_loss	1.0000
9:110972070:TACC:T	donor_loss	1.0000
9:110972071:ACC:A	donor_loss	1.0000
9:110972218:TAC:T	acceptor_gain	1.0000
9:110972218:TACC:T	acceptor_loss	1.0000
9:110972219:ACCT:A	acceptor_loss	1.0000
9:110972220:CCTG:C	acceptor_loss	1.0000
9:110973556:CACCT:C	acceptor_loss	1.0000
9:110973557:ACCTG:A	acceptor_loss	1.0000
9:111037888:C:A	donor_gain	1.0000
9:110875720:CCC:C	acceptor_gain	0.9900
9:110875721:CC:C	acceptor_gain	0.9900
9:110875721:CCC:C	acceptor_gain	0.9900
9:110875722:CC:C	acceptor_gain	0.9900
9:110875723:C:CC	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011489 (9:110876364 T>C), RS1000020812 (9:110903494 C>A), RS1000033182 (9:110959722 T>C), RS1000037000 (9:110923179 G>A), RS1000063633 (9:110873276 T>G), RS1000080075 (9:111022600 AAACTT>A), RS1000095751 (9:111001314 A>G), RS1000101785 (9:110934568 T>C), RS1000115 (9:111032220 G>A), RS1000119577 (9:110941243 A>G), RS1000138445 (9:110977228 T>C), RS1000140482 (9:110955772 A>C), RS1000142636 (9:110995482 T>C), RS1000152634 (9:110934356 C>G), RS1000174195 (9:111036613 C>A,G,T)

Disease associations

OMIM: gene MIM:602282 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST000817_12	Height	1.000000e-09
GCST001137_7	White blood cell count	2.000000e-22
GCST001806_11	Corneal structure	5.000000e-12
GCST002647_32	Height	4.000000e-12
GCST003263_24	Post bronchodilator FEV1 in COPD	2.000000e-06
GCST004129_7	White blood cell count (monocyte)	4.000000e-08
GCST004164_4	Monocyte count	1.000000e-14
GCST004600_79	Eosinophil percentage of white cells	1.000000e-19
GCST004606_11	Eosinophil count	6.000000e-20
GCST004617_170	Eosinophil percentage of granulocytes	1.000000e-16
GCST004623_126	Neutrophil percentage of granulocytes	4.000000e-14
GCST004624_135	Sum eosinophil basophil counts	1.000000e-17
GCST005024_92	Pursuit maintenance gain	3.000000e-06
GCST005146_47	Birth weight	3.000000e-08
GCST005667_17	Central corneal thickness	6.000000e-15
GCST005977_6	Monocyte count	9.000000e-16
GCST008317_9	Central corneal thickness	6.000000e-06
GCST008362_187	Birth weight	2.000000e-14
GCST008363_69	Offspring birth weight	3.000000e-14
GCST008839_340	Height	3.000000e-15
GCST009414_31	Central corneal thickness	6.000000e-11
GCST010232_1	Monocyte count	5.000000e-11
GCST010703_220	Brain morphology (MOSTest)	4.000000e-11
GCST010796_4826	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4827	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST011618_12	Cortical thickness	5.000000e-13
GCST011946_21	White matter hyperintensity volume	7.000000e-06
GCST011947_27	White matter hyperintensity volume	2.000000e-06
GCST011949_36	White matter hyperintensity volume (adjusted for hypertension)	5.000000e-06
GCST011950_29	White matter hyperintensity volume (adjusted for hypertension)	3.000000e-06

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count
EFO:0004345	corneal topography
EFO:0004314	forced expiratory volume
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0008433	pursuit maintenance gain measurement
EFO:0004344	birth weight
EFO:0005213	central corneal thickness
EFO:0005939	parental genotype effect measurement
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0004840	cortical thickness
EFO:0005665	white matter hyperintensity measurement
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3819 (SINGLE PROTEIN), CHEMBL3885601 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 68 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4297270	BMS-986020	2	68

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Lysophospholipid (LPA) receptors

Most potent curated ligand interactions (28 total), top 25:

Ligand	Action	Affinity	Parameter
BMS-986020	Antagonist	8.9	pIC50
ACT-1016-0707	Antagonist	8.54	pIC50
LPA	Full agonist	8.3	pEC50
BMS-986278	Antagonist	8.16	pKB
ONO-3080573	Antagonist	7.96	pIC50
AM966	Antagonist	7.8	pIC50
VPC32183	Antagonist	7.75	pKi
ONO-9910539	Antagonist	7.66	pIC50
ONO-9780307	Antagonist	7.57	pIC50
CpX	Agonist	7.3	pKi
SAR100842	Antagonist	7.3	pIC50
mianserin	Antagonist	7.0	pIC50
Ki16425	Antagonist	6.9	pIC50
VPC12249	Antagonist	6.86	pKi
ONO-7300243	Antagonist	6.8	pIC50
NAEPA	Partial agonist	6.71	pEC50
oleoyl-thiophosphate	Partial agonist	6.71	pEC50
2-oleoyl-LPA	Agonist	6.7	pEC50
UCM-05194	Agonist	6.62	pEC50
CpY	Agonist	6.3	pEC50
T13	Partial agonist	6.3	pEC50
amitriptyline	Antagonist	6.22	pIC50
alkyl OMPT	Agonist	6.2	pEC50
syn-BrP-LPA	Antagonist	6.19	pIC50
AM095	Antagonist	6.1	pIC50

Binding affinities (BindingDB)

597 measured of 629 human assays (629 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[[3-(3-fluorophenyl)propyl-[4-(2-methoxyphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	0.3 nM	US-9464060: Compounds
4-[[[4-(2-fluorophenoxy)benzoyl]-[3-(3-fluorophenyl)propyl]amino]methyl]benzoic acid	IC50	0.4 nM	US-9464060: Compounds
4-[[[4-(2-fluorophenoxy)benzoyl]-[3-(2-fluorophenyl)propyl]amino]methyl]benzoic acid	IC50	1 nM	US-9464060: Compounds
4-[[[4-(2-fluorophenoxy)benzoyl]-[(2-phenylcyclopropyl)methyl]amino]methyl]benzoic acid	IC50	1 nM	US-9464060: Compounds
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-1-(4-fluoropyridin-2-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	1 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
1-(5-cyanopyridin-2-yl)-N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	1 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide	IC50	1.3 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
4-[[[4-(2-fluorophenoxy)benzoyl]-[(4-methoxyphenyl)methyl]amino]methyl]benzoic acid	IC50	2 nM	US-9464060: Compounds
4-[[[4-(2-methoxyphenoxy)benzoyl]-(3-phenylpropyl)amino]methyl]benzoic acid	IC50	2 nM	US-9464060: Compounds
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-3-(2-isopropylphenyl)-1-(2-(sulfamoylamino)ethyl)azetidine-3-carboxamide	IC50	2 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
1-(2-(3-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2-oxoethyl)cyclobutane-1-carboxylic acid	IC50	2 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
methyl 1-(5-(3-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)pyrimidin-2-yl)cyclopropane-1-carboxylate	IC50	2 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-1-(3-fluoropyridin-4-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	2 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-1-(5-fluoropyrimidin-4-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	2 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
1-(5-cyanopyrimidin-2-yl)-N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	2 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
1-(2-(1H-tetrazol-1-yl)acetyl)-N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-4-(2-isopropylphenyl)piperidine-4-carboxamide	IC50	2 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(5-chloro-3-(difluoromethoxy)pyridin-2-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide	IC50	2 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(5-bromo-3-(difluoromethoxy)pyridin-2-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide	IC50	2 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
(R)-N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-1-((R)-(2-hydroxypropyl)glycyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	3 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
ethyl-3-(4-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-4-(2-isopropylphenyl)piperidin-1-yl)-3-oxopropanoate	IC50	3 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-1-(5-fluoropyrimidin-2-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	3 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-3-(2-isopropylphenyl)-1-(2-methylpyrimidin-4-yl)azetidine-3-carboxamide	IC50	3 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-3-(3-isopropylpyridin-2-yl)-1-sulfamoylazetidine-3-carboxamide	IC50	3 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N3-(5-chloro-3-(difluoromethoxy)pyridin-2-yl)-N1-cyclopropyl-3-(2-isopropylphenyl)azetidine-1,3-dicarboxamide	IC50	3 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N3-(5-bromo-3-(difluoromethoxy)pyridin-2-yl)-N1-cyclopropyl-3-(2-isopropylphenyl)azetidine-1,3-dicarboxamide	IC50	3 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
4-[[[4-(2-fluorophenoxy)benzoyl]-[(3-methoxyphenyl)methyl]amino]methyl]benzoic acid	IC50	4 nM	US-9464060: Compounds
4-[[cyclopropylmethyl-[4-(2-methoxyphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	4 nM	US-9464060: Compounds
4-[[[4-(2-methoxyphenoxy)benzoyl]-(2,2,2-trifluoroethyl)amino]methyl]benzoic acid	IC50	4 nM	US-9464060: Compounds
3-((3-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidine-1-carbonyl)oxy)-2,2-dimethylpropanoic acid	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2,6-dimethoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(6-ethoxy-2-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
1-(2-cyanoethyl)-N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
methyl 4-(4-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-4-(2-isopropylphenyl)piperidin-1-yl)-4-oxobutanoate	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
methyl (3-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidine-1-carbonyl)-L-alaninate	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
1-(5-cyanopyridin-2-yl)-N-(2-(difluoromethoxy)pyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-3-(2-isopropylphenyl)-1-(4-oxo-4,5-dihydrooxazol-2-yl)azetidine-3-carboxamide	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
3-((3-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)sulfonyl)propanoic acid	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
3-((3-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)sulfonyl)-2,2-dimethylpropanoic acid	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-1-(2-(3-hydroxy-1H-pyrazol-4-yl)acetyl)-4-(2-isopropylphenyl)piperidine-4-carboxamide	IC50	4 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
2-((4-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-4-(2-isopropylphenyl)piperidine-1-carbonyl)oxy)acetic acid	IC50	4.3 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-3-(2-isopropylphenyl)-1-(2-(methylsulfonamido)ethyl)azetidine-3-carboxamide	IC50	4.6 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
4-[[[4-(2-methoxyphenoxy)benzoyl]-propylamino]methyl]benzoic acid	IC50	5 nM	US-9464060: Compounds
methyl 4-[[butyl-[4-(2-methoxyphenoxy)benzoyl]amino]methyl]benzoate	IC50	5 nM	US-9464060: Compounds
1-(((3-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidine-1-carbonyl)oxy)methyl)cyclopropane-1-carboxylic acid	IC50	5 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
Ethyl ((3-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)sulfonyl)glycinate	IC50	5 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-1-(2-hydroxyethyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	5 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-1-(3-hydroxypropyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	5 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
1-(2-aminopropyl)-N-(2-(difluoromethoxy)-6-methylpyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide	IC50	5 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
1-(2-(3-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2-oxoethyl)cyclopropane-1-carboxylic acid	IC50	5 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
2-(4-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-4-(2-isopropylphenyl)piperidine-1-carboxamido)ethyl methacrylate	IC50	5 nM	US-12344597: Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis

ChEMBL bioactivities

715 potent at pChembl≥5 of 759 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.80	IC50	0.16	nM	CHEMBL4165205
9.72	IC50	0.19	nM	CHEMBL4165205
9.52	IC50	0.3	nM	CHEMBL3966526
9.47	Kd	0.34	nM	CHEMBL4175820
9.40	IC50	0.4	nM	CHEMBL3943133
9.40	IC50	0.4	nM	CHEMBL3936755
9.40	IC50	0.4	nM	CHEMBL3966526
9.31	Kd	0.49	nM	CHEMBL4175820
9.13	Kd	0.74	nM	CHEMBL4175820
9.00	IC50	1	nM	CHEMBL3980736
9.00	IC50	1	nM	CHEMBL3972698
9.00	IC50	1	nM	CHEMBL3943133
8.90	Kd	1.26	nM	CHEMBL4175820
8.85	IC50	1.4	nM	CHEMBL5566408
8.80	IC50	1.6	nM	CHEMBL5633614
8.70	IC50	2	nM	CHEMBL3911605
8.70	IC50	2	nM	CHEMBL3936755
8.70	IC50	2	nM	CHEMBL3980736
8.66	IC50	2.2	nM	CHEMBL5571345
8.66	IC50	2.2	nM	CHEMBL5564704
8.63	Kd	2.34	nM	CHEMBL4175820
8.55	EC50	2.8	nM	CHEMBL5072201
8.54	IC50	2.9	nM	CHEMBL5571345
8.54	IC50	2.9	nM	CHEMBL5569817
8.52	IC50	3	nM	CHEMBL5555025
8.52	IC50	3	nM	CHEMBL3900559
8.51	IC50	3.1	nM	CHEMBL5566876
8.48	IC50	3.32	nM	CHEMBL5555025
8.46	IC50	3.5	nM	CHEMBL3975893
8.46	IC50	3.5	nM	CHEMBL5563392
8.43	IC50	3.7	nM	CHEMBL5571605
8.40	IC50	4	nM	CHEMBL3900559
8.40	IC50	4	nM	CHEMBL3945517
8.40	IC50	4	nM	CHEMBL3901720
8.40	IC50	4	nM	CHEMBL4442789
8.40	IC50	4	nM	CHEMBL3920849
8.38	IC50	4.2	nM	CHEMBL5556401
8.35	IC50	4.5	nM	CHEMBL5591868
8.30	IC50	5	nM	CHEMBL3961765
8.30	IC50	5	nM	CHEMBL3920849
8.30	IC50	5	nM	CHEMBL4557434
8.30	IC50	5	nM	CHEMBL3945517
8.30	IC50	5	nM	CHEMBL3910049
8.30	IC50	5	nM	CHEMBL3980174
8.25	Kd	5.6	nM	LYSOPHOSPHATIDIC ACID
8.25	IC50	5.6	nM	CHEMBL5574523
8.24	IC50	5.7	nM	CHEMBL5565581
8.23	IC50	5.9	nM	CHEMBL3976876
8.22	IC50	6	nM	CHEMBL3891550
8.22	Kd	5.96	nM	CHEMBL4168626

PubChem BioAssay actives

383 with measured affinity, of 889 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(2S)-2-(octadecanoylamino)-3-(4-phenylmethoxyphenyl)propyl] dihydrogen phosphate	248286: Inhibition of LPA-induced calcium transients in RH7777 rat hepatoma cells expressing LPA1 receptor	ic50	<0.0001	uM
3-[1-[(2S,3S)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]pyrrol-3-yl]propanoic acid	1349395: Antagonist activity at recombinant human LPA1 expressed in CHO cell membranes pretreated for 24 hrs prior to Fura-2-AM dye addition for 1 hr followed by LPA stimulation measured after 3 mins by fluorescence assay	ic50	0.0002	uM
3-[1-[(2S,3S)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]pyrrol-3-yl]-2,3-ditritiopropanoic acid	1349394: Binding affinity to recombinant human LPA1 expressed in CHO cell membranes measured after 2 hrs at 37 degC by scintillation counting method	kd	0.0003	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-3-(2-propan-2-ylphenyl)-1-sulfamoylazetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0014	uM
1-[[[(1R)-1-(3,5-dimethoxy-4-methylphenyl)ethyl]-(4-phenylbutyl)carbamoyl]amino]-3,3-difluorocyclobutane-1-carboxylic acid	2138540: Antagonist activity at human LPA1 receptor stably expressed in rat RH7777 cells assessed as reduction in LPA-induced intracellular Ca2+ concentration preincubated for 30 mins followed by LPA addition measured by Fluo-4 probe based fluorescence assay	ic50	0.0016	uM
1-[2-[3-[[2-(difluoromethoxy)-6-methyl-3-pyridinyl]carbamoyl]-3-(2-propan-2-ylphenyl)azetidin-1-yl]-2-oxoethyl]cyclobutane-1-carboxylic acid	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0022	uM
N-(2-methoxy-4-methylphenyl)-3-(2-propan-2-ylphenyl)azetidine-3-carboxamide	2089847: Antagonist activity at human LPA1 receptor expressed in Tango EDG2-bla U2OS cells co-expressing beta-arrestin/TEV protease fusion protein and beta-lactamase reporter gene assessed as inhibition of LPA-induced beta-arrestin recruitment preincubated for 30 mins followed by LPA addition and measured after 16 hrs by FRET based fluorescence analysis	ic50	0.0022	uM
trans-(1S,3S)-3-[[6-[5-[[cyclobutylmethyl(methyl)carbamoyl]oxymethyl]-1-methyltriazol-4-yl]-2-methyl-3-pyridinyl]oxy]cyclohexane-1-carboxylic acid	2095676: Antagonist activity at human LPA1 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ec50	0.0028	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-3-(2-propan-2-ylphenyl)-1-[2-(sulfamoylamino)ethyl]azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0029	uM
4-[4-[(2-methoxy-4-methylphenyl)carbamoyl]-4-(2-propan-2-ylphenyl)piperidin-1-yl]-4-oxobutanoic acid	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0030	uM
N-(6-chloro-4-methoxy-3-pyridinyl)-3-(2-propan-2-ylphenyl)-1-sulfamoylazetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0031	uM
N-(2-methoxy-4-methylphenyl)-4-(2-propan-2-ylphenyl)piperidine-4-carboxamide	2089847: Antagonist activity at human LPA1 receptor expressed in Tango EDG2-bla U2OS cells co-expressing beta-arrestin/TEV protease fusion protein and beta-lactamase reporter gene assessed as inhibition of LPA-induced beta-arrestin recruitment preincubated for 30 mins followed by LPA addition and measured after 16 hrs by FRET based fluorescence analysis	ic50	0.0035	uM
5-chloro-2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenylpropyl)amino]methyl]phenoxy]benzoic acid	1320794: Antagonist activity at human LPA1 receptor expressed in CHO cells assessed as reduction in LPA-induced intracellular Ca2+ concentration pretreated with compound followed by LPA addition by fluorescence assay	ic50	0.0035	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-3-(3-propan-2-yl-2-pyridinyl)-1-sulfamoylazetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0037	uM
trans-(1S,3S)-3-[[6-[3-methyl-4-[(2-phenylethylsulfonylamino)methyl]-1,2-oxazol-5-yl]-3-pyridinyl]oxy]cyclohexane-1-carboxylic acid	1570842: Antagonist activity at human LPA1 expressed in CHO cells assessed as reduction in LPA-induced calcium influx incubated for 20 mins	ic50	0.0040	uM
1-[(2S)-2,3-dihydroxypropyl]-N-(2-methoxy-4-methylphenyl)-4-(2-propan-2-ylphenyl)piperidine-4-carboxamide	2089847: Antagonist activity at human LPA1 receptor expressed in Tango EDG2-bla U2OS cells co-expressing beta-arrestin/TEV protease fusion protein and beta-lactamase reporter gene assessed as inhibition of LPA-induced beta-arrestin recruitment preincubated for 30 mins followed by LPA addition and measured after 16 hrs by FRET based fluorescence analysis	ic50	0.0042	uM
1-(2-hydroxyacetyl)-N-(2-methoxy-4-methylphenyl)-4-(2-propan-2-ylphenyl)piperidine-4-carboxamide	2089847: Antagonist activity at human LPA1 receptor expressed in Tango EDG2-bla U2OS cells co-expressing beta-arrestin/TEV protease fusion protein and beta-lactamase reporter gene assessed as inhibition of LPA-induced beta-arrestin recruitment preincubated for 30 mins followed by LPA addition and measured after 16 hrs by FRET based fluorescence analysis	ic50	0.0045	uM
trans-(1S,3S)-3-[[6-[4-[[(3-fluorophenyl)methoxycarbonylamino]methyl]-3-methyl-1,2-oxazol-5-yl]-3-pyridinyl]oxy]cyclohexane-1-carboxylic acid	1570842: Antagonist activity at human LPA1 expressed in CHO cells assessed as reduction in LPA-induced calcium influx incubated for 20 mins	ic50	0.0050	uM
1-[2-[3-[[2-(difluoromethoxy)-6-methyl-3-pyridinyl]carbamoyl]-3-(2-propan-2-ylphenyl)azetidin-1-yl]-2-oxoethyl]cyclopropane-1-carboxylic acid	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0056	uM
[(2R)-2-hydroxy-3-phosphonooxypropyl] (Z)-octadec-9-enoate	1650459: Binding affinity to LPA1 receptor (unknown origin) by cell-based backscattering interferometry	kd	0.0056	uM
4-[3-[[2-(difluoromethoxy)-6-methyl-3-pyridinyl]carbamoyl]-3-(2-propan-2-ylphenyl)azetidin-1-yl]-2,2-dimethyl-4-oxobutanoic acid	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0057	uM
4-chloro-2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenylpropyl)amino]methyl]phenoxy]benzoic acid	1320794: Antagonist activity at human LPA1 receptor expressed in CHO cells assessed as reduction in LPA-induced intracellular Ca2+ concentration pretreated with compound followed by LPA addition by fluorescence assay	ic50	0.0059	uM
2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenyl-2,3-ditritiopropyl)amino]methyl]phenyl]acetic acid	1349390: Binding affinity to recombinant human LPA1 expressed in CHO cell membranes measured after 2 hrs by scintillation counting method	kd	0.0060	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-1-(3-hydroxypropyl)-3-(2-propan-2-ylphenyl)azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0064	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-1-[2-(3-oxo-1,2-dihydropyrazol-4-yl)acetyl]-3-(2-propan-2-ylphenyl)azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0064	uM
1-[4-[4-[3-methyl-4-[[(1R)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid	2095676: Antagonist activity at human LPA1 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ec50	0.0067	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-1-[2-(methanesulfonamido)ethyl]-3-(2-propan-2-ylphenyl)azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0071	uM
4-[3-[[2-(difluoromethoxy)-6-methyl-3-pyridinyl]carbamoyl]-3-(2-propan-2-ylphenyl)azetidin-1-yl]-2,2-dimethylbutanoic acid	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0077	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-1-(methylsulfamoyl)-3-(2-propan-2-ylphenyl)azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0078	uM
dihydroxy-(2-methoxy-3-octadecoxypropoxy)-sulfanylidene-lambda5-phosphane	733691: Agonist activity at human LPA1 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay	ec50	0.0083	uM
1-(2-aminoethyl)-N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-3-(2-propan-2-ylphenyl)azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0089	uM
1-(2-hydroxyethyl)-N-(2-methoxy-4-methylphenyl)-4-(2-propan-2-ylphenyl)piperidine-4-carboxamide	2089847: Antagonist activity at human LPA1 receptor expressed in Tango EDG2-bla U2OS cells co-expressing beta-arrestin/TEV protease fusion protein and beta-lactamase reporter gene assessed as inhibition of LPA-induced beta-arrestin recruitment preincubated for 30 mins followed by LPA addition and measured after 16 hrs by FRET based fluorescence analysis	ic50	0.0089	uM
trans-(1S,3S)-3-[[6-[4-[[(4-fluorophenyl)methoxycarbonylamino]methyl]-3-methyl-1,2-oxazol-5-yl]-3-pyridinyl]oxy]cyclohexane-1-carboxylic acid	1570842: Antagonist activity at human LPA1 expressed in CHO cells assessed as reduction in LPA-induced calcium influx incubated for 20 mins	ic50	0.0090	uM
3-[3-[[2-(difluoromethoxy)-6-methyl-3-pyridinyl]carbamoyl]-3-(2-propan-2-ylphenyl)azetidin-1-yl]-3-oxopropanoic acid	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0094	uM
4-[3-[(2-methoxy-4-methylphenyl)carbamoyl]-3-(2-propan-2-ylphenyl)azetidin-1-yl]-4-oxobutanoic acid	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0100	uM
dihydroxy-[(2S)-2-methoxy-3-octadecoxypropoxy]-sulfanylidene-lambda5-phosphane	733691: Agonist activity at human LPA1 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay	ec50	0.0101	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-1-[2-(2-hydroxyethylamino)acetyl]-3-(2-propan-2-ylphenyl)azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0103	uM
4-[4-[[2-(difluoromethoxy)-6-methyl-3-pyridinyl]carbamoyl]-4-(2-propan-2-ylphenyl)piperidin-1-yl]-4-oxobutanoic acid	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0104	uM
4-[3-[[2-(difluoromethoxy)-6-methyl-3-pyridinyl]carbamoyl]-3-(2-propan-2-ylphenyl)azetidin-1-yl]butanoic acid	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0108	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-3-(2-propan-2-ylphenyl)-1-(3-sulfamoylpropanoyl)azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0111	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-1-[(2R)-2,3-dihydroxypropyl]-3-(2-propan-2-ylphenyl)azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0111	uM
sodium (2-heptadecoxy-3-methoxypropoxy)-hydroxy-oxido-sulfanylidene-lambda5-phosphane	733691: Agonist activity at human LPA1 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay	ec50	0.0111	uM
sodium [1-[hydroxy(oxido)phosphinothioyl]oxy-3-methoxypropan-2-yl] octadecanoate	733691: Agonist activity at human LPA1 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay	ec50	0.0122	uM
5-[3-[[2-(difluoromethoxy)-6-methyl-3-pyridinyl]carbamoyl]-3-(2-propan-2-ylphenyl)azetidin-1-yl]-5-oxopentanoic acid	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0129	uM
2-[1-[(2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)-hydroxymethyl]-5-phenylpentyl]pyrrol-3-yl]acetic acid	1349373: Antagonist activity at recombinant human LPA1 expressed in CHO cells assessed as reduction in LPA-induced intracellular calcium level pretreated followed by LPA addition by Fura-2-AM dye based fluorescence assay	ic50	0.0130	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-1-[2-(methanesulfonamido)acetyl]-3-(2-propan-2-ylphenyl)azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0134	uM
N-[2-(difluoromethoxy)-6-methyl-3-pyridinyl]-3-(2-propan-2-ylphenyl)azetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0136	uM
[(2S)-3-dihydroxyphosphinothioyloxy-2-methoxypropyl] octadecanoate	733691: Agonist activity at human LPA1 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay	ec50	0.0147	uM
N-(6-chloro-4-methoxy-3-pyridinyl)-3-(3-propan-2-yl-2-pyridinyl)-1-sulfamoylazetidine-3-carboxamide	2089881: Antagonist activity at LPAR1 in Tango EDG2-bla U2OS human cells assessed as LPA-induced beta-arrestin-2 recruitment pretreated with compound for 30 mins followed by LPA-induction and measured after 16 hrs by FRET assay	ic50	0.0147	uM
N-(2-methoxy-4-methylphenyl)-4-(2-propan-2-ylphenyl)oxane-4-carboxamide	2089847: Antagonist activity at human LPA1 receptor expressed in Tango EDG2-bla U2OS cells co-expressing beta-arrestin/TEV protease fusion protein and beta-lactamase reporter gene assessed as inhibition of LPA-induced beta-arrestin recruitment preincubated for 30 mins followed by LPA addition and measured after 16 hrs by FRET based fluorescence analysis	ic50	0.0147	uM

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	7
lysophosphatidic acid	increases response to substance, affects binding, decreases reaction, decreases expression, affects localization (+2 more)	3
trichostatin A	affects cotreatment, decreases expression	2
Benzo(a)pyrene	increases mutagenesis, decreases methylation, increases methylation	2
Estradiol	affects expression, affects binding, increases expression	2
Lead	decreases expression, affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	increases expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	affects expression, affects cotreatment	1
N-benzyloxycarbonylprolylprolinal	decreases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
monomethylarsonous acid	increases expression	1
lipopolysaccharide, E. coli O26-B6	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
belinostat	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
MRK 003	decreases expression	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
asparanin A	decreases expression	1

ChEMBL screening assays

120 unique, capped per target: 79 functional, 41 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1064669	Binding	Binding affinity to LPA1	Structure-based drug design identifies novel LPA3 antagonists. — Bioorg Med Chem
CHEMBL1065839	Functional	Agonist activity at LPA1 expressed in human chem1 cells assessed as intracellular calcium mobilization by FLIPR assay	Synthesis, in vitro structure-activity relationship, and in vivo studies of 2-arylthiazolidine-4-carboxylic acid amides as anticancer agents. — Bioorg Med Chem

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 2 spontaneously immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1XD	Abcam A-549 LPAR1 KO	Cancer cell line	Male
CVCL_D2BN	Abcam HCT 116 LPAR1 KO	Cancer cell line	Male
CVCL_D7TQ	Ubigene A-549 LPAR1 KO	Cancer cell line	Male
CVCL_D8PB	Ubigene HCT 116 LPAR1 KO	Cancer cell line	Male
CVCL_D9IN	Ubigene HEK293 LPAR1 KO	Transformed cell line	Female
CVCL_KV13	cAMP Hunter CHO-K1 EDG2 Gi	Spontaneously immortalized cell line	Female
CVCL_KW93	PathHunter CHO-K1 EDG2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA22	PathHunter U2OS EDG2 Activated GPCR Internalization	Cancer cell line	Female
CVCL_ZK17	Tango EDG2-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.