LPA Receptor
Lysophosphatidic acid (LPA) consists of an acyl chain at the sn-1 (or sn-2) position of a glycerol backbone and a phosphate head group. LPA activates at least six G-coupled protein receptors (LPA1–6) stimulating different signaling pathways through heterotrimeric G proteins such as Gi/0, G12/13, Gq/11, and Gs. The lysophosphatidic acid (LPA) is a lipid acting at the intersection of fibrosis and cancer development. LPA's pro-oncogenic (pro-proliferative, pro-angiogenic, anti-apoptotic, and pro-migration / invasion properties have been recently evidenced. Increased secretion of LPA can be triggered by tissue damage (including surgery, chemotherapy and radiation therapy) and/or by chronic inflammation. In parallel of its pro-fibrotic activity, LPA has also been repeatedly described as an oncogenic promoter, responsible of tumour initiation, growth, and metastasis. LPA could stimulate production of VEGF, interleukine-8 (IL-8) and urokinase plasminogen activator (uPA) in ovarian cancer cells, enhancing hyper-vascularisation processes finally leading to metastases.
LPAR1-4 stimulate the mitogenic pathway Ras-Ras-Raf-MEK-ERK pathway, and the pro-survival PI3K pathway. LPAR1-3 and LPAR5 stimulate the invasion/migration thought the activation of the Rho pathway. The Rac Pathway, also involved in invasion/migration, can be stimulated by LPAR1-4 as well. In vitro, LPA significantly increased ovarian cancer cell invasion, partly through the down-regulation of invasion negative regulators (tissue inhibitor of metalloproteinases (TIMPs)). In vivo, LPA stimulated ovarian tumour metastasis, but this phenomenon could be significantly inhibited using an inhibitor of PI3K (an effector in the LPA signalling pathway).
References
1.Rancoule C,et al. Oncotarget. 2017;8(26):43543–43554.
2.Valdés-Rives SA,et al. Mediators Inflamm. 2017;2017:9173090.
LPAR1-4 stimulate the mitogenic pathway Ras-Ras-Raf-MEK-ERK pathway, and the pro-survival PI3K pathway. LPAR1-3 and LPAR5 stimulate the invasion/migration thought the activation of the Rho pathway. The Rac Pathway, also involved in invasion/migration, can be stimulated by LPAR1-4 as well. In vitro, LPA significantly increased ovarian cancer cell invasion, partly through the down-regulation of invasion negative regulators (tissue inhibitor of metalloproteinases (TIMPs)). In vivo, LPA stimulated ovarian tumour metastasis, but this phenomenon could be significantly inhibited using an inhibitor of PI3K (an effector in the LPA signalling pathway).
References
1.Rancoule C,et al. Oncotarget. 2017;8(26):43543–43554.
2.Valdés-Rives SA,et al. Mediators Inflamm. 2017;2017:9173090.
GPCR/G Protein
ACAT(3)
Angiotensin Receptor(27)
Antibacterial(471)
Bombesin Receptor(11)
Bradykinin Receptor(18)
Calcium Channel(137)
cAMP(9)
Cannabinoid Receptor(69)
CaSR(17)
CGRP Receptor(14)
Chemokine Receptor(104)
Cholecystokinin Receptor(17)
CRF Receptor(13)
Dopamine Receptor(145)
Endothelin Receptor(20)
FFAR(5)
Galanin Receptor(1)
GHSR(16)
Glucagon Receptor(36)
GPCR19(7)
GPR119(3)
Hedgehog (Hh)(27)
Histamine Receptor(110)
Imidazoline Receptor(1)
Leukotriene Receptor(9)
LHR(1)
LPA Receptor(12)
Lysophospholipid Receptor(13)
mAChR(25)
MCHR(6)
Melanocortin Receptor(22)
Melatonin Receptor(5)
mGluR(11)
Motilin Receptor(4)
Neurokinin Receptor(34)
Neuropeptide Y Receptor(36)
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Orexin Receptor(14)
Other Targets(3)
OXTR(2)
P2Y Receptor(8)
PAR(24)
Platelet-activating Factor Receptor(2)
Prostaglandin Receptor(60)
PTH Receptor(1)
S1P Receptor(22)
SGLT(22)
Somatostatin Receptor(11)
Urotensin Receptor(4)
Vasopressin Receptor(16)
LPA Receptor
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TAK-615
catalog no : M28841
cas no: 1664335-55-0
TAK-615 is commonly used to study pulmonary fibrosis and is a negative allosteric modulator of LPA1 receptors. -
H2L5186303
catalog no : M27634
cas no: 139262-76-3
H2L5186303 is an LPA2 antagonist and can be used in studies about asthma treatment. -
Radioprotectin-1
catalog no : M26412
cas no: 1622006-09-0
Radioprotectin-1 is a selective agonist of LPA2 with EC50 of 25 nM for murine LPA2 GPCR and exerts radioprotective and radiomitigative action. -
H2L 5765834
catalog no : M24386
cas no: 420841-84-5
H2L 5765834 is a lysophosphatidic acid receptors antagonist. -
AM095 free acid
catalog no : M22924
cas no: 1228690-36-5
AM095 (free acid) is a potent LPA1 receptor antagonist (IC50s: 0.98 and 0.73 μM for recombinant human or mouse LPA1).In vitro, AM095 was a potent LPA receptor antagonist because it inhibited GTPγS binding to Chinese hamster ovary (CHO) cell membranes overexpressing recombinant human or mouse LPA with IC values of 0.98 and 0.73 μM, respectively, and exhibited no LPA agonism.