An LPA1 receptor antagonist
BMS 986020 is an antagonist of lysophosphatidic acid receptor 1 (LPA1; Kb = 0.0067 ?M).1 It is selective for LPA1 over LPA3 in CHO cells expressing the human receptors (IC50s = 0.3 and >1 ?M, respectively).2 BMS 986020 also inhibits organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, the bile salt export pump (BSEP), multidrug resistant protein 3 (MDR3), multidrug resistance-associated protein 3 (MRP3), and MRP4 (IC50s = 0.17, 0.57, 4.8, 7.5, 22, and 6.2 ?M, respectively).1 It reduces bleomycin-induced lung fibrosis in rats when administered at a dose of 30 mg/kg twice per day. BMS 986020 (225 and 500 mg/kg per day) decreases total biliary bile acid levels and induces bile duct hyperplasia, cholangitis, and cholestasis in monkeys.3 It decreases infarct volume and neurological deficits in a mouse model of ischemic stroke induced by transient middle cerebral artery occlusion (MCAO) when administered at a dose of 5 mg/kg.4
1.Cheng, P.T.W., Kaltenbach, R.F., III, Zhang, H., et al.Discovery of an oxycyclohexyl acid lysophosphatidic acid receptor 1 (LPA1) antagonist BMS-986278 for the treatment of pulmonary fibrotic diseasesJ. Med. Chem.64(21)15549-15581(2021) 2.Hutchinson, J.H., Seiders, T.J., Wang, B., et al.Polycyclic antagonists of lysophosphatidic acid receptors(2010) 3.Sivaraman, L., Gill, M., Nelson, D.M., et al.Structure dependence and species sensitivity of in vivo hepatobiliary toxicity with lysophosphatidic acid receptor 1 (LPA1) antagonistsToxicol. Appl. Pharmacol.115846(2021) 4.Gaire, B.P., Sapkota, A., and Choi, J.W.BMS-986020, a specific LPA1 antagonist, provides neuroprotection against ischemic stroke in miceAntioxidants (Basel)9(11)1097(2020)
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