Harris C John, Stevens Adrian P
BioFocus DPI, Chesterford Research Park, Saffron Walden, Essex, CB10 1XL, UK.
Drug Discov Today. 2006 Oct;11(19-20):880-8. doi: 10.1016/j.drudis.2006.08.013. Epub 2006 Sep 7.
In the post-genomic era, if all proteins in a gene family can putatively be identified, how can drug discovery effectively tackle so many novel targets that might lack structural and small-molecule inhibitory data? In response, chemogenomics, a new approach that guides drug discovery based on gene families, has been developed. By integrating all information available within a protein family (sequence, SAR data, protein structure), chemogenomics can efficiently enable cross-SAR exploitation, directed compound selection and early identification of optimum selectivity panel members. This review examines recent developments in chemogenomics technologies and illustrates their predictive capabilities with successful examples from two of the major protein families: protein kinases and G-protein-coupled receptors.
在后基因组时代，如果一个基因家族中的所有蛋白质都可以被推定识别，那么药物研发如何能有效地应对如此多可能缺乏结构和小分子抑制数据的新靶点呢？作为回应，化学基因组学这一基于基因家族指导药物研发的新方法应运而生。通过整合蛋白质家族内所有可用信息（序列、构效关系数据、蛋白质结构），化学基因组学能够有效地实现跨构效关系利用、定向化合物筛选以及早期识别最佳选择性筛选成员。本文综述了化学基因组学技术的最新进展，并通过来自两个主要蛋白质家族——蛋白激酶和G蛋白偶联受体的成功案例来说明其预测能力。
