BMS 986278

BMS 986278 is an antagonist of lysophosphatidic acid receptor 1 (LPA1, Kb = 0. µM). It is selective for LPA1 over a panel of 44 receptors, ion channels, and enzymes when used at concentrations ranging from 30 to 150 µM, including the bile salt export pump (BSEP), multidrug resistance protein 3 (MDR3), multidrug resistance-associated protein 3 (MRP3), MRP4, organic anion transporting polypeptide 1B1 (OATP1B1), and OATP1B3 (IC50s = >100, >100, 66, 47, 36, and 10 µM, respectively). BMS 986278 inhibits LPA-induced histamine release in mice in a dose-dependent manner. Oral administration of BMS 986278 (3 and 10 mg/kg) reduces bleomycin-induced lung fibrosis in rats. Unlike BMS 986020 (Cay-22049), BMS 986278 does not induce bile duct hyperplasia, cholangitis, or cholestasis in cynomolgus monkeys. InChI: InChI=1S/C22H31N5O5/c1-5-11-26(3)22(30)31-13-18-20(24-25-27(18)4)17-9-10-19(14(2)23-17)32-16-8-6-7-15(12-16)21(28)29/h9-10,15-16H,5-8,11-13H2,1-4H3,(H,28,29)/t15-,16-/m0/s1 InChIKey: UEUNDURNLYLSNB-HOTGVXAUSA-N SMILES: O=C(N(C)CCC)OCC1=C(C(N=C2C)=CC=C2O[C@@H](CCC3)C[C@H]3C(O)=O)N=NN1C