Medicinal Chemistry, Taros Chemicals GmbH & Co. KG, Emil-Figge-Straße 76a, 44227, Dortmund, Germany; Department of Biomedical Engineering and Institute for Complex Molecular Systems, Technische Universiteit Eindhoven, Den Dolech 2, 5612, AZ, Eindhoven, the Netherlands.
Medicinal Chemistry, Taros Chemicals GmbH & Co. KG, Emil-Figge-Straße 76a, 44227, Dortmund, Germany.
Eur J Med Chem. 2019 Apr 1;167:76-95. doi: 10.1016/j.ejmech.2019.01.084. Epub 2019 Feb 5.
Protein-protein interactions (PPIs) cover a very wide range of biological functions and consequently have become one of the favourite targets for new therapeutic strategies. PPIs are strongly characterised by an intricate and dynamic network of surface interactions occurring between two or more proteins. Because of the complexity of these interactions, many strategies have been applied with the aim to find selective modulators for a specific protein-protein complex. During the last decade, fragment-based approaches have served many drug discovery programs with an impressive increment of contributions, gaining a remarkable role in PPIs modulators' development. In this review, we detail the successful fragment-to-clinical candidate evolutions related to PPI modulation. An overview on the physico-chemical properties of both fragment hits and lead compounds will be presented together with a statistical analysis of their distribution.
蛋白质-蛋白质相互作用（PPIs）涵盖了非常广泛的生物功能，因此已成为新治疗策略的首选目标之一。PPIs 的特点是两个或多个蛋白质之间发生的复杂而动态的表面相互作用网络。由于这些相互作用的复杂性，许多策略已被应用于寻找针对特定蛋白质-蛋白质复合物的选择性调节剂。在过去的十年中，基于片段的方法为许多药物发现计划提供了支持，为贡献的增加做出了令人印象深刻的贡献，在 PPI 调节剂的开发中发挥了重要作用。在这篇综述中，我们详细介绍了与 PPI 调节相关的从片段到临床候选药物的成功进化。将介绍片段命中和先导化合物的物理化学性质概述，并对其分布进行统计分析。
