Razaxaban hydrochloride

Razaxaban hydrochloride (BMS 561389 hydrochloride) is a highly potent, selective and orally active factor Xa inhibitor with a Ki 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 Ki of 540 nM. Razaxaban hydrochloride has strongly antithrombotic activity[1].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> Thrombin

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

Ki: 0.19 nM (Factor Xa); 540 nM (Thrombin)[1]

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 Ki of 0.16 nM[1].

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]. Animal Model: Rabbit arterio-venous shunt thrombosis model[1] Dosage: 0.21 mg/kg/hour, 0.7 mg/kg/hour, 2.1 mg/kg/hour, 9.4 mg/kg/hour Administration: Intravenous injection Result: Inhibited thrombus formation in a dose-dependent manner with an ID50 of 1.6 µmol/kg/h.

[1]. Quan ML, et al. Discovery of 1-(3'-aminobenzisoxazol-5'-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2'-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide hydrochloride (razaxaban), a highly potent, selective, and orally bioavailable factor Xa inhibitor. J Med Chem. 2005 Mar 24;48(6):1729-44.