Chemogenomics Laboratory, Research Unit on Biomedical Informatics, Institut Municipal d’Investigació Mèdica and Universitat Pompeu Fabra, Parc de Recerca Biomèdica (PRBB), Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.
Curr Top Med Chem. 2011;11(15):1956-63. doi: 10.2174/156802611796391285.
The degree of applicability of chemogenomic approaches to protein families depends on the accuracy and completeness of pharmacological data and the corresponding level of pharmacological similarity observed among their protein members. The recent public domain availability of pharmacological data for thousands of small molecules on 204 G protein-coupled receptors (GPCRs) provides a firm basis for an in-depth cross-pharmacology analysis of this superfamily. The number of protein targets included in the cross-pharmacology profile of the different GPCRs changes significantly upon varying the ligand similarity and binding affinity criteria. However, with the exception of muscarinic receptors, aminergic GPCRs distinguish themselves from the rest of the members in the family by their remarkably high levels of pharmacological similarity among them. Clusters of non-GPCR targets related by cross-pharmacology with particular GPCRs are identified and the implications for unwanted side-effects, as well as for repurposing opportunities, discussed.
化学基因组学方法在蛋白质家族中的适用性程度取决于药理学数据的准确性和完整性，以及观察到的蛋白质成员之间的相应药理学相似性水平。最近，数千种小分子对 204 个 G 蛋白偶联受体 (GPCR) 的药理学数据在公共领域中可用，为对这个超级家族进行深入的交叉药理学分析提供了坚实的基础。在不同的 GPCR 中，交叉药理学特征中包含的蛋白质靶标数量在改变配体相似性和结合亲和力标准时会发生显著变化。然而，除了毒蕈碱受体之外，胺能 GPCR 与家族中的其他成员区别开来，它们之间的药理学相似性非常高。与特定 GPCR 通过交叉药理学相关的非 GPCR 靶标簇被识别出来，并讨论了它们对不良副作用的影响，以及重新利用的机会。
