Discovery of Eliquis?/Apixaban, a Novel Factor Xa Anticoagulant

Promulgator:郭剑Date:2020-01-10Hits:13

Thrombosis is the leading cause of death in developed countries. There is a significant need for novel antithrombotics with an improved safety profile to replace Warfarin which has been in use for ~60 years and has significant bleeding issues. Currently the antithrombotic market is the fastest growing one, more than even oncology. Factor Xa is at the junction of the intrinsic and extrinsic pathways of the coagulation cascade. Preclinical data has demonstrated that blocking FXa is an effective approach for anticoagulation with improved safety profile. Utilizing structure-based drug design tools, focused screening, and ADME-T innovations, we at Bristol-Myers Squibb had discovered a novel class of potent, selective and orally bioavailable Factor Xa inhibitors culminating in Eliquis®/Apixaban. Eliquis® was recently approved by FDA and named the “Best New Medicine of 2012” by Med Ad News. During the optimization process, we have also discovered the powerful Chan-Lam Coupling reaction of copper promoted C-X bond cross-coupling via boronic acids, a complementary reaction to the Nobel prize Suzuki-Miyaura Coupling reaction. In addition, we have pioneered the first rational use of halogen bonding in structure-based drug design.

Patrick Y. LAM Patrick received his Ph.D. from the University of Rochester (Dr. Louis Friedrich) and was a postdoctoral fellow in UCLA (Prof. Mike Jung and the late Prof. Don Cram, 1987 Nobel Laureate). Patrick has over 27 years of research experience. His expertise is in innovations in structure-based drug design, ADME, focused libraries, molecular recognition and nucleic acid therapeutics to deliver biopharma clinical candidates with novel profiles. Patrick is internationally known as the co-discoverer of the powerful Chan-Lam Coupling Reaction. Patrick has worked with CROs successfully and productively for ten years. Patrick has authored 93 papers/reviews/book chapters and is an inventor on 36 patents/patent applications.