4月6日Distinguished Prof. Patrick Y. S. Lam学术报告预告

    Title: Structure-Based Discovery of Eliquis^®/Apixaban, a Novel Factor Xa Anticoagulant

    Time: 2:00 p.m., April 6, 2017

    Place: Round Gallery Hall, Run Run Shaw Building, Zhaohui Campus, Zhejiang University of Technology

    Speechmaker: Distinguished Prof. Patrick Y. S. Lam

    Patrick Lam 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 in chemistry). He is currently a medicinal chemistry and drug discovery consultant at Lam Drug Discovery Consulting, LLC, Distinguished Professor of Chemistry at Baruch S. Blumberg Institute and Adjunct Professor at Drexel University College of Medicine. He recently retired from a chemistry director position of Bristol-Myers Squibb Co. He joined DuPont in 1984 and moved to BMS in 2001. In recent years, he has been involved with antivirals (HBV capsid, surface antigen and cccDNA inhibitors, Dengue Fever inhibitors, HIV-DCSIGN blockers), antithrombotics (FXIa and FXa inhibitors as anticoagulants; P2Y1 and PAR4 antagonists as antiplatelet agents), PCSK9 antisense oligonucleotide (ASO) therapeutics, prodrugs and carbohydrates. He has >30 years of drug discovery experience. His expertise is in innovations in structure-based drug design, ADME-T, focused libraries, molecular recognition and nucleic acid therapeutics to deliver biopharma clinical candidates with novel profiles.

Abstract:

    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. 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. Eliquis^® is currently a “block-buster” drug with annual sales of ~$4B. 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 C-C bond Coupling reaction. In addition, at the molecular recognition frontier, we have pioneered the first rational use of halogen bonding in structure-based drug design.