Screening for molecular glues – Challenges and opportunities

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 in...

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Bibliographic Details
Published in:SLAS discovery 2024-03, Vol.29 (2), p.100136-100136, Article 100136
Main Authors: Holdgate, Geoffrey A., Bardelle, Catherine, Berry, Sophia K., Lanne, Alice, Cuomo, Maria Emanuela
Format: Article
Language:English
Subjects:
Competition
Degradation
Molecular glue
Protein proximity
Stabilisation
Ubiquitination
Undruggable targets
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Summary: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.
ISSN:2472-5552
2472-5560
DOI:10.1016/j.slasd.2023.12.008