Laird Ellen R, Blake James F
Array BioPharma Inc, 3200 Walnut Street, Boulder, CO 80301, USA.
Curr Opin Drug Discov Devel. 2004 May;7(3):354-9.
Parallel synthesis and structure-aided design have begun to converge in the process of drug discovery. Virtual screening using X-ray crystal structures of therapeutic targets to front-load a high-throughput screen or to establish a tractable collection for lower throughput assays has become a standard practice in many lead generation settings. The application of similar techniques for increasing the likelihood of including active compounds in a focused combinatorial library is a natural progression that is beginning to be recognized. In this review, we will cover recent reports of small, focused libraries designed for specific therapeutic targets, and for which X-ray crystallographic data is available.
在药物研发过程中，平行合成与结构辅助设计已开始融合。利用治疗靶点的X射线晶体结构进行虚拟筛选，以便在高通量筛选前进行预富集，或为低通量分析建立易于处理的化合物库，这在许多先导化合物发现的场景中已成为标准做法。将类似技术应用于提高在聚焦组合库中纳入活性化合物的可能性是一种自然的发展趋势，并且已开始得到认可。在本综述中，我们将涵盖针对特定治疗靶点设计的小型聚焦库的近期报道，且这些库都有X射线晶体学数据。
