Razaxaban (hydrochloride)

Razaxaban hydrochloride (BMS 561389 hydrochloride) is a highly potent, selective and orally active factor Xa inhibitor with a K_i of 0.19 nM. Razaxaban hydrochloride exhibits excellent selectivity (>5000-fold) for factor Xa over other related serine proteases. Razaxaban hydrochloride is also a potent thrombin inhibitor with a K_i of 540 nM. Razaxaban hydrochloride has strongly antithrombotic activity^[1]. IC50 & Target: Ki: 0.19 nM (Factor Xa); 540 nM (Thrombin)^[1] In Vitro: Razaxaban (compound 11d) shows good Caco-2 permeability^[1].
The anticoagulant activity of Razaxaban (compound 11d) is evaluated in the in vitro human plasma activated partial thromboplastin time (aPTT) and human prothrombin time (PT) assays. Razaxaban shows a doubling of aPTT and PT at 6.1 µM and 2.1 µM, respectively. The human and rabbit plasma protein binding are found to be 90.5% and 93.4%, respectively, using equilibrium dialysis. Razaxaban is found to have similar affinity in the rabbit factor Xa assay with a K_i of 0.16 nM^[1]. In Vivo: Razaxaban (Compound 11d; 0.21-9.4 mg/kg/hour; intravenous injection) inhibits thrombus formation in a dose-dependent manner with an ID₅₀ of 1.6 µmol/kg/h in the rabbit arterio-venous shunt thrombosis model^[1].