基于片段的药物设计.pptVIP

FRAGMENT- BASED DRUG DESIGN Yemane MengistuMichigan State UniversityJanuary 30, 2008 Annual Research and Development Expense Drug Discovery Process Creating a Library Creating a Library Using Ugi Chemistry Creating a Thymidinyl Ugi Library Thymidinyl Ugi Library High-throughput Screening (HTS) What types of compounds become leads from an HTS? A Typical Drug Discovery Cascade HTS Fragnomics: Fragment Based Drug Design MW of Average HTS Hits and Fragments Fragnomics: Fragment Based Drug Design Fragnomics: Fragment Based Drug Design What Qualifies Compounds to be Fragments? What Qualifies Compounds to be Fragments? What Qualifies Compounds to be Fragments? Some Common Drug-Based Fragments Conventional HTS vs. Fragonomics Based on Central Scaffold Conventional (HTS) Drug Design Conventional (HTS) and Fragment Based Drug Design Fragment Based Drug Design Fragment Based Drug Design Fragment Based Drug Design Fragment Based Drug Design Application of Fragment based drug design Library for the Protein kinase inhibitor Library for the Protein kinase inhibitor Library of protein kinase inhibitor Fragment-Based Design : Protein Kinase Inhibition Application of Fragment Based Drug Design Application of Fragment Based Drug Design Application of Fragment Based Drug Design Application of Fragment Based Drug Design Application of Fragment based Drug Design Preparation of Disulfide-Containing Library Members Synthesis of Sulfonyl Libraries Thymidylate Synthase Inhibitor Thymidylate Synthase Inhibitor Application of Fragment Based Drug Design Tethering with Extenders-dynamically Assembling Fragments Caspase-3 Summary Acknowledgements Prof. Kevin D. Walker Prof. Babak Borhan Prof. Bill Wulff Prof. Bob Hausinger Dr. Philip J. Hajduk , Abbott Laboratories Lab members:,Mark, Irosha, Washington, Danielle, Behnaz Friends: Khassay, Mercy, Rahman, Anil, Munmun, Luis Maly, D.J., Choong, D.J., and Ellman, J.A. Proc.Natl.Acad.Sci.USA. 2000,97,2419-2424 1. Protein kinase i