Darexaban

Darexaban (YM150) is a potent, selective and orally active factor Xa (FXa) inhibitor with an IC50 of 54.6 nM. Darexaban shows high selectivity against other related serine proteases, such as trypsin, thrombin, and kallikrein. Darexaban has anticoagulant and antithrombotic effects[1][2][3].

Darexaban is an oral direct factor Xa (FXa) inhibitor that is rapidly and extensively metabolized into its glucuronide conjugate (YM-222714) post-administration. Darexaban competitively and selectively inhibits human FXa, and also inhibits the prothrombin activation induced by prothrombinase complex or whole blood clot with similar potency to free FXa[2].

In mice, Darexaban inhibits FXa activity in plasma with an ED50 value of 24.8 mg/kg. Darexaban prolonges prothrombin time (PT) at 3 mg/kg[2]. In a pulmonary thromboembolism (PE) mouse model, Darexaban dose-dependently reduces the mortality rate, significantly so at 10 mg/kg[2]. In a FeCl3-induced venous thrombosis (VT) mouse model, Darexaban (0.3-10 mg/kg) dose-dependently decreases the thrombus protein content, significantly so at doses of 3 mg/kg or higher[2].

[1]. Fukushi Hirayama, et al. Discovery of N-[2-hydroxy-6-(4-methoxybenzamido)phenyl]-4- (4-methyl-1,4-diazepan-1-yl)benzamide (darexaban, YM150) as a potent and orally available factor Xa inhibitor. J Med Chem. 2011 Dec 8;54(23):8051-65.
[2]. Seiji Kaku, et al. Darexaban: anticoagulant effects in mice and human plasma in vitro, antithrombotic effects in thrombosis and bleeding models in mice and effects of anti-inhibitor coagulant complex and recombinant factor VIIa. Thromb Res. 2013 May;131(5):450-6.
[3]. Milan Remko, et al. Theoretical Study of Molecular Structure and Physicochemical Properties of Novel Factor Xa Inhibitors and Dual Factor Xa and Factor IIa Inhibitors. Molecules. 2016 Feb 4;21(2):185.