Schmid Molly B
Keck Graduate Institute, 535 Watson Drive, Claremont, CA 91711, USA.
Biochem Pharmacol. 2006 Mar 30;71(7):1048-56. doi: 10.1016/j.bcp.2005.12.024. Epub 2006 Feb 3.
Over the past decade, the sequences of microbial genomes have accumulated, changing the strategies for the discovery of novel anti-infective agents. Targets have become plentiful, yet new antimicrobial agents have been slow to emerge from this effort. In part, this reflects the long discovery and development times needed to bring new drugs to market. In addition, bottlenecks have been revealed in the antimicrobial drug discovery process at the steps of identifying good leads, and optimizing those leads into drug candidates. The fruit of structural genomics may provide opportunities to overcome these bottlenecks and fill the antimicrobial pipeline, by using the tools of structure guided drug discovery (SGDD).
在过去十年中,微生物基因组序列不断积累,这改变了新型抗感染药物的发现策略。靶点变得丰富多样,但通过这种方式发现的新型抗菌药物却迟迟未能出现。部分原因在于,将新药推向市场需要漫长的发现和开发时间。此外,抗菌药物发现过程在识别优质先导化合物以及将这些先导化合物优化为候选药物的环节中暴露出了瓶颈。结构基因组学的成果或许能提供机会,通过运用结构导向药物发现(SGDD)工具来克服这些瓶颈并充实抗菌药物研发渠道。