抗癌药研究.pptVIP

Anti-cancer Drug Discovery and Development Outline Anti-cancer drug discovery process The approach to anti-cancer drug discovery Identification and validation of target Computer aided drug design Small Moleculars screening through HTS Metabolic and Physicochemical Profiling of drug Cancer resistance Anti-cancer drug discovery process Modern molecular biology and genomics/proteomics to identify and validate new therapeutic targets Combinatorial chemistry for the efficient generation of structural diversity and for rapid production of a library of structural analogues based on an identified lead compound and optimization, enhanced structural biology and molecular modeling techniques for rational drug design Robotic high-throughput screening against structurally diverse chemical libraries to discover lead drugs High-throughput pharmacokinetics assays, the use of surrogate end points to monitor pharmacodynamics throughout thediscovery and development process, particularly involving genomics (e.g., nucleic acid microassays) and proteomics The approach to anti-cancer drug discovery cell-based screening Targeting the specific molecular lesions Cell-based screening 1.cell-based cytotoxicity assays: random high-throughput screening of synthetic compounds and natural products, based on anti-proliferative effects 2. synthetic compounds and natural products belong to DNA-damaging agents with a low therapeutic index, Not target the molecular lesions responsible for malignant transformation NCI: highly chemo-sensitive P388 leukemia cell line Target-based screening for anti-cancer drug discovery Identification and validation of target Emerging targets Drug design and HTS Identification and validation of target Genomics analytic technology: microarray analysis, high-throught RNAi, Ambion, Inc. Cenix BioScience Proteomics analytic technology:affinity chromatography and mass spectrometry X-omics analytic technology Epig