Fry David C, Vassilev Lyubomir T
Structural Chemistry Group, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
J Mol Med (Berl). 2005 Dec;83(12):955-63. doi: 10.1007/s00109-005-0705-x. Epub 2005 Nov 11.
An increasing number of protein-protein interactions have been identified as potential intervention points for the development of anticancer agents. However, such systems have historically been considered high-risk targets due to the relatively large interaction surfaces involved in protein-protein binding. This characterization has to be reexamined as progress has been made recently in identifying small-molecule inhibitors of several protein-protein systems in oncology including the p53-MDM2 interaction. This review presents a survey of protein-protein interactions that have been identified as potential oncology targets and evaluates their attractiveness in terms of drug discovery. The analysis focuses primarily on the structural characteristics of the participating binding sites, particularly the dimensions of the sites. Known ligands are also examined, especially with regard to their druglikeness.
越来越多的蛋白质-蛋白质相互作用已被确定为抗癌药物开发的潜在干预点。然而，由于蛋白质-蛋白质结合所涉及的相互作用表面相对较大，这类系统在历史上一直被视为高风险靶点。随着最近在鉴定包括p53-MDM2相互作用在内的几种肿瘤学蛋白质-蛋白质系统的小分子抑制剂方面取得进展，这种特征必须重新审视。本综述对已被确定为潜在肿瘤学靶点的蛋白质-蛋白质相互作用进行了概述，并从药物发现的角度评估了它们的吸引力。分析主要集中在参与结合位点的结构特征上，特别是位点的尺寸。还研究了已知的配体，尤其是它们的类药性。
