【摘要】 计算机辅助药物设计已普遍应用于药物研发过程,大大加快了药物开发的速度。特别是全新药物设计方法可以用于识别作用于特异性靶点的全新配体结构。全新药物设计常用软件有LUDI,LigBuilder,LeapFrog,SPROUT和SYNOPSIS等,常用方法有片段连接、片段生长、侧链替换和骨架跃迁等。全新药物设计方法在一些抗癌化合物,如纺锤体驱动蛋白抑制剂、血管内皮生长因子抑制剂、亲环蛋白A抑制剂和BRAF抑制剂等的发现方面,已经发挥了重要作用。综述全新药物设计方法与常用软件,并举例讨论其在新型抗癌药物领域中的应用。更多还原

【Abstract】 Computer aided drug design had become part of the drug discovery process,greatly improved the speed of drug development compared with traditional drug finding methods.In particular,the de novo drug design method could be used to identify ligands with novel structure for a special target.Through computer simulation,researchers could find new ideas about how to change a compound to improve the drug properties or how to assemble some fragments to generate candidates which be drug-like,synthetically accessible and high affinity for a target.The common software of de novo design included LUDI,MCSS,LigBuilder,SPROUT,SYNOPSIS,BREED,LeapFrog and RACHEL,etc.The methods were fragments link and grow,side chain replacement,parent molecule evolve,template,scaffold hopping and so on.Discovery and development of cancer drugs had been revolutionized over the last decade.De novo drug design methods had already played a significant role in the discovery of some anticancer compounds such as kinesin spindle protein inhibitors,vascular endothelial growth factor inhibitors,cyclophilin A inhibitors,cell division cycle protein CDC25 inhibitors and BRAF inhibitors.The common software and methods of de novo drug design were summarized in this review and their applications in antitumor drug design were discussed.更多还原