FXIa inhibitor SB-01 is a potent, selective, allosteric inhibitor of human factor XIa (FXIa) inhibitor with IC50 of 130 nM, displays potent antithrombotic activity.
SB-01 displays little to no activity (30-800-fold selective) against closest serine proteases FIIa, FXa, FIXa, FXIIa, and plasma kallikrein (P.Kal).
SB-01 inhibits FXIa activation of its natural protein substrate hFIX with IC50 of 150 nM.
SB-01 selectively prolongs activated partial thromboplastin time (APTT) over prothrombin time (PT), shows no impairment in FVII, FXIII, protein C (PrC), protein S (PrS), antithrombin (AT) or heparin cofactor II (HCII) in plasma.
SB-01 impacted all aspects of thrombus formation, including initiation of thrombus formation, rate of thrombus maturation and thrombus strength, in a concentration-dependent manner in human whole blood thromboelastography (TEG) studies.
SB-01 inhibits rodent arterial and venous thrombosis at doses of 6 and 3 mg/kg, respectively, preventing deep vein thrombosis in animals with lung cancer, does not significantly increase mouse tail bleeding time or blood loss.