BMS-986141

BMS-98614 is an orally active, selective thrombin receptor protease-activated receptor-4 (PAR-4) antagonist with an IC50 value of 0.4 nM. BMS-98614 has excellent antithrombotic effect[1][2].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> GPCR/G Protein >> Protease-Activated Receptor (PAR)

PAR4:0.4 nM (IC50)

BMS-986141 (compound 49) (0-1 μM) inhibits platelet aggregation induced by PAR4 agonist peptide with an IC50 value of 2.2 nM[1].

BMS-986141 (compound 49) shows a slight but significant prolongation of KBT (kidney bleeding time) and demonstrates excellent anti-thrombotic efficacy at 0.5 mg/kg in cynomolgus monkey[1][2]. Animal Model: Monkey arterial thrombosis (AT) and mesenteric bleeding time (MBT) models[2] Dosage: 0.05, 0.1, 0.5 mg/kg Administration: p.o., 2 hours Result: Inhibited PAR4-AP-induced platelet aggregation in human and monkey blood with IC50 of 1.8 and 1.3 nM, respectively. Reduced the thrombus weight by 36%, 63% and 88% at concentrations of 0.05, 0.1 and 0.5 mg/kg, respectively in AT model. Increased MBT by 1.2 times. Animal Model: Rat, dog and monkey[1] Dosage: 0.5, 1, 2 mpk Administration: i.v., 0.5 mpk, 10 min or p.o., 2 mpk for rat, 1 mpk for dog and monkey Result: The pharmacokinetic parameters of BMS-986141 (compound 49) Parameters rat dog monkey t1/2(h) 3.7 ± 0.4 13 75 ± 12 CL (mL/min/kg) 14.3 ± 0.4 8.5 12 ± 2 Vss(L/kg) 2.7 ± 0.3 2.7 14 ± 5 F (%) 31 25 36

[1]. E Scott Priestley, et al. Discovery of Two Novel Antiplatelet Clinical Candidates (BMS-986120 and BMS-986141) That Antagonize Protease-Activated Receptor 4. J Med Chem. 2022 Jul 14;65(13):8843-8854.

[2]. P Wong, et al. Favorable therapeutic index of an orally-active small-molecule antagonist of the platelet protease-activated receptor-4, BMS-986141, compared with the P2Y12 antagonist ticagrelor in cynomolgus monkeys. European Heart Journal, Volume 41, Issue Supplement_2, November 2020.