Hajduk Philip J
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
Mol Interv. 2006 Oct;6(5):266-72. doi: 10.1124/mi.6.5.8.
It has been nearly ten years since the introduction of SAR by NMR and the advent of fragment-based drug design. During this time, we have gained a tremendous amount of knowledge about protein druggability, the limits of chemical diversity, and crafting high-affinity ligands from low molecular weight, weakly binding leads. This review will describe the concept of fragment-based drug design, discuss why it works, and illustrate the power of the approach with two case studies on the design of potent inhibitors of matrix metalloproteinases and Bcl-2 family proteins.
自通过核磁共振（NMR）引入片段亲和性（SAR）以及基于片段的药物设计出现以来，已经过去了近十年。在此期间，我们在蛋白质可成药性、化学多样性的局限性以及从低分子量、弱结合先导化合物构建高亲和力配体方面获得了大量知识。本综述将描述基于片段的药物设计概念，讨论其奏效的原因，并通过两个关于基质金属蛋白酶和Bcl-2家族蛋白强效抑制剂设计的案例研究来说明该方法的威力。
