Holdgate Geoffrey A, Bardelle Catherine, Berry Sophia K, Lanne Alice, Cuomo Maria Emanuela
Hit Discovery, Discovery Sciences, R&D, AstraZeneca, Alderley Park, UK.
High-throughput Screening, Discovery Sciences, R&D, AstraZeneca, Alderley Park, UK.
SLAS Discov. 2024 Mar;29(2):100136. doi: 10.1016/j.slasd.2023.12.008. Epub 2023 Dec 15.
Molecular glues are small molecules, typically smaller than PROTACs, and usually with improved physicochemical properties that aim to stabilise the interaction between two proteins. Most often this approach is used to improve or induce an interaction between the target and an E3 ligase, but other interactions which stabilise interactions to increase activity or to inhibit binding to a natural effector have also been demonstrated. This review will describe the effects of induced proximity, discuss current methods used to identify molecular glues and introduce approaches that could be adapted for molecular glue screening.
分子胶是小分子,通常比PROTACs小,并且通常具有改善的物理化学性质,旨在稳定两种蛋白质之间的相互作用。最常见的是,这种方法用于改善或诱导靶标与E3连接酶之间的相互作用,但也已证明其他稳定相互作用以增加活性或抑制与天然效应物结合的相互作用。本综述将描述诱导邻近效应,讨论目前用于鉴定分子胶的方法,并介绍可适用于分子胶筛选的方法。