BMS-262084

BMS-262084 is a potent, selective and irreversible inhibitor of factor XIa, with an IC50 of 2.8 nM against human factor XIa. BMS-262084 also inhibits human tryptase (IC50=5 nM). BMS-262084 exhibits antithrombotic effects[1][2].

Signaling Pathways >> Metabolic Enzyme/Protease >> Ser/Thr Protease

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> Factor Xa

IC50: 2.8 nM (factor XIa), 5 nM (tryptase)[1]

BMS-262084 shows more than 70-fold selectivity for human factor XIa (IC50=2.8 nM) over tryptase, trypsin, urokinase, plasma kallikrein, plasmin, yhrombin (factor IIa) and Factor IXa (IC50=0.005, 0.05, 0.542, 0.55, 1.7,10.5, and 17.4 μM, respectively)[1]. BMS-262084 (1-100 μM) doubles the activated thromboplastin time in human and rat plasma at 0.14 and 2.2 μM, respectively[1].

BMS-262084 (2-12 mg/kg + 2-12 mg/kg/h; i.v.) reduces carotid artery thrombus weight and improves both vessel patency and integrated flow in rats[1]. Animal Model: Male Sprague Dawley rats (310-390 g) were induced venous thrombosis by FeCl2[1] Dosage: 2 mg/kg + 2 mg/kg/h, 6 mg/kg + 6 mg/kg/h, 12 mg/kg + 12 mg/kg/h Administration: I.v. 10 min before FeCl2 application Result: Reduced carotid artery thrombus weight by 73% at the dose of 12 mg/kg + 12 mg/kg/h. Improved both vessel patency and integrated flow.

[1]. Schumacher WA, et, al. Antithrombotic and hemostatic effects of a small molecule factor XIa inhibitor in rats. Eur J Pharmacol. 2007 Sep 10;570(1-3):167-74.

[2]. Qian X, et, al. A stereoselective synthesis of BMS-262084, an azetidinone-based tryptase inhibitor. J Org Chem. 2002 May 31;67(11):3595-600.