Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Université Paris Diderot, Sorbonne Paris Cité, UMRS 973 Inserm, Paris 75013, France; Inserm, U973, Paris 75013, France.
Drug Discov Today. 2016 Jan;21(1):48-57. doi: 10.1016/j.drudis.2015.09.011. Epub 2015 Oct 3.
Most of the small molecules that have been identified thus far to modulate protein-protein interactions (PPIs) are inhibitors. Another promising way to interfere with PPI-associated biological processes is to promote PPI stabilization. Even though PPI stabilizers are still scarce, stabilization of PPIs by small molecules is gaining momentum and offers new pharmacological options. Therefore, we have performed a literature survey of PPI stabilization using small molecules. From this, we propose a classification of PPI stabilizers based on their binding mode and the architecture of the complex to facilitate the structure-based design of stabilizers.
迄今为止，已发现大多数能调节蛋白质-蛋白质相互作用（PPIs）的小分子是抑制剂。另一种有前途的干扰与 PPI 相关的生物过程的方法是促进 PPI 稳定。尽管小分子 PPI 稳定剂仍然稀缺，但小分子稳定 PPI 的方法正在兴起，并提供了新的药理学选择。因此，我们对使用小分子稳定 PPI 进行了文献调查。在此基础上，我们根据小分子的结合模式和复合物的结构提出了 PPI 稳定剂的分类，以促进稳定剂的基于结构的设计。
