〔筛选途径的药物发现 Screening Based Drug Discovery 药物设计学 李炜 wei-li@fudan.edu.cn 复旦大学药学院 药物化学教研室 September 17, 2018
September 17, 2018 药物设计学 复旦大学药学院 药物化学教研室 李 炜 wei-li@fudan.edu.cn 筛选途径的药物发现 Screening Based Drug Discovery
New medicines discovered by Janssen’ s team OH N H2c N haloperidol fentanyl N、CH 3 N(CH3 N HO F CI risperidone loperamide More than 80 new medicines(absolute world record), at the wide range of his inventions in psychopharmacology, neuropharmacology, gastroenterology, cardiology parasitology, virology, immunology, anaesthesiology, and analgesia
New medicines discovered by Janssen’s team haloperidol risperidone fentanyl loperamide More than 80 new medicines (absolute world record), at the wide range of his inventions in psychopharmacology, neuropharmacology, gastroenterology, cardiology, parasitology, virology, immunology, anaesthesiology, and analgesia 4
Classic of Phenotypic screening Iterative evolution process Conception A lead compd Test feedback A picture of ppropriate Synthesis bioassay Bioassay structure activity Unmet medical evaluation relationship need Active in least 3 /5 authentic exo-vivo or in vivo pharmacological models purpose? or When fit for its Judgment E xperience Workup Creativity Imagination Aesthetic intuition A concept-driven project
Classic of Phenotypic screening Conception A lead compd Appropriate bioassay Unmet medical need Iterative evolution process Synthesis Bioassay evaluation Test feedback A picture of structureactivity relationship Active in least 3/5 authentic exo-vivo or in vivo pharmacological models When Fit for its purpose? Judgment Experience Imagination Aesthetic intuition —— A concept-driven project Workup Creativity When Fit for its purpose? Judgment Experience Imagination Aesthetic intuition 5
筛选途径需要解决的基本问题 结构多样性( Diversity) I.转化医学( ranslational medicine, from bench to bedside)
筛选途径需要解决的基本问题 I. 结构多样性（Diversity） II. 转化医学（Translational Medicine, from bench to bedside）
药物设计基本原理 多样性 Diversity 药物分子的多样性 天然产物提取分离、 合成以及半合成 合成化合物的筛选 组合化学 View of PubChem chemical space Reymond, J L, ACS Chem. Neurosci. 3(9): 649657
药物设计基本原理—— 多样性 Diversity • 药物分子的多样性 • 天然产物提取分离、 合成以及半合成 • 合成化合物的筛选 • 组合化学 View of PubChem chemical space Reymond, J.L, ACS Chem. Neurosci. 3 (9): 649–657 11