药物的生物活化-原理，常规分析方法和影响.pdf

Bioactivation (Metabolic Activation) of Drugs – Principles, Protocols and Impacts (药物的生物活化 原理，常规分析方法和影响) 张洲鹏 博士 文波 博士 1 Outlines 1. Introduction (介绍) 2. Bioactivation of drugs and metabolism-dependent drug-induced toxicities (药物的生物活化和药物代谢引起的的毒性) 3. Functional group metabolism to reactive metabolites ( 由相关药物的化学结构代谢为具有反应活性的代谢物 4. Experimental strategies to detect reactive metabolites (具有反应活性代谢物的常用分析检测方法) a. Common trapping agents for reactive metabolites (常用诱捕剂) b. LC/MS analysis of protein and DNA adducts (蛋白质和DNA加合物的质谱分析) c. Analytical strategies for high-throughput screening of reactive metabolites (高通量筛选反应性代谢物的分析检测方法) 5. Assessment of exposure and magnitude of reactive metabolite formation (具有反应活性代谢物的半定量分析与方法) a. In vitro covalent protein binding assays (体外共价蛋白结合实验与步骤) b. In vivo covalent protein binding assays (体内共价蛋白结合实验与步骤) 6. Structural alerts and rational drug design (药物分子结构预警与合理药物设计) 7. Data interpretation and risk mitigation strategies (数据与风险评估方法) 8. Panel discussion and Q&A (小组讨论与问答) 2 1. Introduction (介绍) Discovery and development of new drugs involve: chemistry, biology, pharmacology, toxicology, safety, process chemistry, formulation, regulatory affairs, clinical research, manufacturing, marketing, etc. 3 The 10 biggest R&D spenders worldwide in 2013 Volkswagen Samsung Intel Microsoft Roche Novartis Toyota J&J Google Merck $ (Billions) 13.5 13.4 10.6 10.4 10.0 9.9 9.1 8.2 8.0 7.5 %