Assessing the scaffold diversity of screening libraries
Assessing the scaffold diversity of screening libraries
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DOI：
10.1021/ci050352v
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发表时间：
2006-03-01
影响因子：
5.6
通讯作者：
Rognan, D
中科院分区：
文献类型：
--
作者：
Krier, M;Bret, G;Rognan, D
药物化学家传统上实现了化学多样性和随后的化合物收购的评估，虽然最近的一项研究表明，专家在审查大型数据集通常是不一致的。为了分析商业上可获得的筛选集合的支架多样性，我们已经开发了一个通用的工作流程，其目的在于（1）识别药物样化合物，（2）通过最大共同子结构将它们聚类（3）独立于其大小测量由每个筛选集合编码的支架多样性，最后（4）将所有公共子结构合并到一个无冗余的支架库中，该支架库可以容易地通过结构和拓扑查询来浏览。从12个商业来源中的240万种化合物开始，可以鉴定出四类文库：大型和中型组合文库（低支架多样性）、多样性文库（中等多样性，中等大小）和高度多样性文库（高多样性，低大小）。可以搜索由支架文库覆盖的化学空间以优先化支架聚焦文库。
Medicinal chemists have traditionally realized assessments of chemical diversity and subsequent compound acquisition, although a recent study suggests that experts are usually inconsistent in reviewing large data sets. To analyze the scaffold diversity of commercially available screening collections, we have developed a general workflow aimed at (1) identifying druglike compounds, (2) clustering them by maximum common substructures (scaffolds), (3) measuring the scaffold diversity encoded by each screening collection independently of its size, and finally (4) merging all common substructures in a nonredundant scaffold library that can easily be browsed by structural and topological queries. Starting from 2.4 million compounds out of 12 commercial sources, four categories of libraries could be identified: large- and medium-sized combinatorial libraries (low scaffold diversity), diverse libraries (medium diversity, medium size), and highly diverse libraries (high diversity, low size). The chemical space covered by the scaffold library can be searched to prioritize scaffold-focused libraries.