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...