Kubinyi H
University of Heidelberg, Weisenheim am Sand, Germany.
Ernst Schering Res Found Workshop. 2006(58):1-19. doi: 10.1007/978-3-540-37635-4_1.
Chemogenomics is a new strategy in drug discovery which, in principle, searches for all molecules that are capable of interacting with any biological target. Because of the almost infinite number of drug-like organic molecules, this is an impossible task. Therefore chemogenomics has been defined as the investigation of classes of compounds (libraries) against families of functionally related proteins. In this definition, chemogenomics deals with the systematic analysis of chemical-biological interactions. Congeneric series of chemical analogs are probes to investigate their action on specific target classes, e.g., GPCRs, kinases, phosphodiesterases, ion channels, serine proteases, and others. Whereas such a strategy developed in pharmaceutical industry almost 20 years ago, it is now more systematically applied in the search for target- and subtype-specific ligands. The term "privileged structures" has been defined for scaffolds, such as the benzodiazepines, which very often produce biologically active analogs in a target family, in this case in the class of G-protein-coupled receptors. The SOSA approach is a strategy to modify the selectivity of biologically active compounds, generating new drug candidates from the side activities of therapeutically used drugs.
化学基因组学是药物研发中的一种新策略，原则上它要寻找所有能够与任何生物靶点相互作用的分子。由于类药物有机分子数量几乎无穷无尽，这是一项不可能完成的任务。因此，化学基因组学被定义为针对功能相关蛋白家族对各类化合物（文库）进行的研究。在此定义中，化学基因组学涉及对化学 - 生物相互作用的系统分析。同类化学类似物系列是用于研究其对特定靶点类别（如G蛋白偶联受体、激酶、磷酸二酯酶、离子通道、丝氨酸蛋白酶等）作用的探针。尽管这种策略大约在20年前就在制药行业中发展起来，但现在它在寻找靶点和亚型特异性配体方面得到了更系统的应用。“优势结构”一词已针对某些骨架结构定义，比如苯二氮䓬类，这类结构常常能在一个靶点家族（在这种情况下是G蛋白偶联受体类别）中产生生物活性类似物。SOSA方法是一种改变生物活性化合物选择性的策略，它从治疗性药物的副作用中生成新的候选药物。
