Systematic Analysis of Public Domain Compound Potency Data Identifies Selective Molecular Scaffolds across Druggable Target Families
Systematic Analysis of Public Domain Compound Potency Data Identifies Selective Molecular Scaffolds across Druggable Target Families
复制标题
DOI：
10.1021/jm9014229
复制
发表时间：
2010-01-28
影响因子：
7.3
通讯作者：
Bajorath, Juergen
中科院分区：
文献类型：
--
作者：
Hu, Ye;Wassermann, Anne Mai;Bajorath, Juergen
产生目标家族选择性化合物的分子支架在药物研究中具有高度的兴趣。对于是否存在对给定靶家族和/或靶具有先验选择性的化学型以及如何鉴定它们，在该领域仍然存在相当大的争论。现有的数据告诉我们什么？我们提出了一个系统的和全面的选择性为中心的分析公共领域。靶-配体相互作用。在目前可用的活性化合物中鉴定了200多种分子支架，其对已建立的靶家族具有选择性。这些支架的一个子集被发现产生的化合物具有高度的选择性，在密切相关的目标之间的个别目标。这些支架目前在批准的药物中代表性不足。
Molecular scaffolds that yield target family-selective compounds are of high interest in pharmaceutical research. There continues to be considerable debate in the field as to whether chemotypes with a priori selectivity for given target families and/or targets exist and how they might be identified. What do currently available data tell us? We present a systematic and comprehensive selectivity-centric analysis of public domain. target-ligand interactions. More than 200 molecular scaffolds are identified in currently available active Compounds that are selective for established target families. A subset of these scaffolds is found to produce compounds with high selectivity for individual targets among closely related ones. These scaffolds are Currently underrepresented in approved drugs.