Compound 3f (Janssen)

Compound 3f is a potent, orally bioavailable small molecule inhibitor of Factor XIa (FXIa), developed by Janssen Research & Development. Discovered through structure-based drug design (SBDD) and the exploitation of nonclassical interactions—such as halogen bonding and pi-stacking—to improve potency and oral bioavailability while reducing polar atom count, Compound 3f represents a next-generation approach to anticoagulation. By targeting FXIa, a key component of the intrinsic coagulation pathway, the drug aims to prevent pathological thrombosis while minimizing the risk of bleeding, a significant limitation of current anticoagulants like warfarin and direct oral anticoagulants (DOACs) that target Factor Xa or thrombin. Preclinical studies have demonstrated that Compound 3f possesses high binding affinity (Ki = 0.17 nM) and favorable pharmacokinetic properties, including significant oral bioavailability across multiple species (rat, dog, and monkey). It has shown dose-dependent antithrombotic efficacy in animal models, such as the rabbit arteriovenous shunt model, without significantly prolonging bleeding time.

Other names

FXIa inhibitor 3f