Sperandio Olivier, Villoutreix Bruno O, Morelli Xavier, Roche Philippe
Molécules thérapeutiques in silico (MTi), université Paris Diderot, Inserm UMR-S973, 35, rue Hélène Brion, 75205 Paris Cedex 13, France.
Centre de recherche en cancérologie de Marseille (CRCM), CNRS UMR7258 ; Inserm U1068 ; institut Paoli-Calmettes ; université d'Aix-Marseille UM105, 27, boulevard Lei Roure,13009, Marseille, France.
Med Sci (Paris). 2015 Mar;31(3):312-9. doi: 10.1051/medsci/20153103017. Epub 2015 Apr 8.
The identification of complete networks of protein-protein interactions (PPI) within a cell has contributed to major breakthroughs in understanding biological pathways, host-pathogen interactions and cancer development. As a consequence, PPI have emerged as a new class of promising therapeutic targets. However, they are still considered as a challenging class of targets for drug discovery programs. Recent successes have allowed the characterization of structural and physicochemical properties of protein-protein interfaces leading to a better understanding of how they can be disrupted with small molecule compounds. In addition, characterization of the profiles of PPI inhibitors has allowed the development of PPI-focused libraries. In this review, we present the current efforts at developing chemical libraries dedicated to these innovative targets.
细胞内蛋白质-蛋白质相互作用(PPI)完整网络的识别,已促成了在理解生物途径、宿主-病原体相互作用及癌症发展方面的重大突破。因此,PPI已成为一类新的、有前景的治疗靶点。然而,它们在药物研发项目中仍被视为具有挑战性的靶点类别。近期的成功使得能够对蛋白质-蛋白质界面的结构和物理化学性质进行表征,从而更好地理解如何用小分子化合物破坏这些界面。此外,PPI抑制剂谱的表征促进了专注于PPI的文库的开发。在本综述中,我们介绍了目前致力于开发针对这些创新靶点的化学文库的工作。