AM966

AM966 is an orally bioavailable, potent, and selective antagonist of the lysophosphatidic acid receptor 1 (LPA1) that has an IC50 value of 17 nM in a calcium assay using CHO cells transfected with the human LPA1 receptor. It is selective for LPA1 over the LPA2, LPA3, LPA4, and LPA5 receptors (IC50s = 1,700, 1,600, 7,700, and 8,600 nM for LPA2-5, respectively). In vitro, AM966 inhibits LPA-induced lung fibroblast cell chemotaxis (IC50 = 181 nM), increases barrier permeability, activates RhoA, and induces phosphorylation of myosin light chain and vascular endothelium cadherin (VE-cadherin). At a dose of 30 mg/kg in mice, it reduces inflammation, tissue fibrosis, and vascular permeability following bleomycin-induced lung injury. AM966 also blocks amitriptyline-induced ERK1/2, CREB, and insulin growth factor-1 receptor (IGF-IR) phosphorylation in vitro.Formal Name: 4'-[4-[[[(1R)-1-(2-chlorophenyl)ethoxy]carbonyl]amino]-3-methyl-5-isoxazolyl]-[1,1'-biphenyl]-4-acetic acid. CAS Number: 1228690-19-4. Molecular Formula: C27H23ClN2O5. Formula Weight: 490.9. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS(pH 7.2) (1:4): 0.2 mg/ml, Ethanol: 2.5 mg/ml. lambdamax: 296 nm. SMILES: O=C(O)CC(C=C1)=CC=C1C(C=C2)=CC=C2C3=C(NC(O[C@H](C)C4=C(Cl)C=CC=C4)=O)C(C)=NO3. InChi Code: InChI=1S/C27H23ClN2O5/c1-16-25(29-27(33)34-17(2)22-5-3-4-6-23(22)28)26(35-30-16)21-13-11-20(12-14-21)19-9-7-18(8-10-19)15-24(31)32/h3-14,17H,15H2,1-2H3,(H,29,33)(H,31,32)/t17-/m1/s1. InChi Key: WWQTWEWAPUCDDZ-QGZVFWFLSA-N.