Scatton Bernard
1 sente de Saint Clair, 91940 Gometz le Chatel, France.
J Soc Biol. 2009;203(3):249-69. doi: 10.1051/jbio:2009030. Epub 2009 Oct 16.
This paper reviews the process used in the pharmaceutical industry to discover new innovative drugs originating from medicinal chemistry or biotherapeutics. After a rapid description of the global Research and Development process (preclinical and clinical studies), the different steps involved specifically in the Discovery Research phase (from the initiation of the research program to the proposal of a candidate for development) are analysed in detail. As far as compounds originating from medicinal chemistry are concerned, we discuss the choice of the biological target (molecular or cellular) and its functional validation, the process used for the screening of chemical libraries and the generation of chemical hits, the hit-to-lead process and finally the chemical optimisation of the leads into drug candidates which will be proposed for preclinical and clinical development. As far as biotherapeutics are concerned, the process used for the generation and manufacturing of humanized naked or conjugated monoclonal antibodies and recombinant therapeutic proteins is discussed in detail.
本文回顾了制药行业中发现源自药物化学或生物治疗学的新型创新药物所采用的过程。在快速描述全球研发过程（临床前和临床研究）之后，详细分析了发现研究阶段（从研究项目启动到提出开发候选药物）具体涉及的不同步骤。就源自药物化学的化合物而言，我们讨论了生物靶点（分子或细胞）的选择及其功能验证、化学文库筛选和化学活性物质生成所采用的过程、活性物质到先导物的过程，以及最终将先导物化学优化为将被提出用于临床前和临床开发的候选药物的过程。就生物治疗学而言，详细讨论了人源化裸抗体或偶联单克隆抗体以及重组治疗性蛋白质的生成和制造过程。
