On sampling of fragment space
On sampling of fragment space
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DOI：
10.1021/jm0700316
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发表时间：
2007-07-12
影响因子：
7.3
通讯作者：
Makara, Gergely M.
中科院分区：
文献类型：
--
作者：
Makara, Gergely M.
多年来，基于片段的先导发现已经成熟为用于先导产生的高通量筛选（HTS）的有吸引力的替代方案。已经报道了几种用于筛选通常为10（3）-10（4）片段的文库的技术。在这项工作中，实际的成功率，可以预期从片段样库的筛选进行了调查，通过查询药物化学数据库的几个程序与虚拟库创建的商业可用的试剂或商业可用的片段库。结果表明，在与常用HTS方案相似的筛选条件下，可以一致地从实际可获得的化合物组中鉴定出比通常在当今基于片段的筛选中发现的更有效的命中。
Fragment-based lead discovery has over the years matured into an attractive alternative to high-throughput screening (HTS) for lead generation. Several techniques for screening libraries of typically 10(3)-10(4) fragments have been reported. In this work, the practical success rates that can be expected from the screening of fragment-like libraries was investigated via interrogating medicinal chemistry databases for several programs with virtual libraries created from commercially available reagents or with libraries of commercially available fragments. The results suggest that hits more potent than typically discovered in today's fragment-based screens can consistently be identified from realistically accessible compound sets under screening conditions similar to commonly used HTS protocols.