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@article{Gray:2026:10.1021/jacs.5c12299,
author = {Gray, JL and Xiao, Z and Rogga, VV and Zhang, X and Tate, EW},
doi = {10.1021/jacs.5c12299},
journal = {J Am Chem Soc},
pages = {4791--4814},
title = {From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.},
url = {http://dx.doi.org/10.1021/jacs.5c12299},
volume = {148},
year = {2026}
}
TY - JOUR
AB - Molecular glues represent a new paradigm in drug discovery, stabilizing novel protein-protein interactions between two proteins to elicit targeted cellular outcomes. Historically discovered through serendipity, molecular glue identification is becoming increasingly systematic. In this perspective, we discuss the current advances and challenges of this field, highlighting the transition toward rational discovery through the convergence of four complementary approaches. Innovations in library design and screening platforms are expanding access to glue-relevant chemical space, guided by a deeper mechanistic understanding of proximity-induced pharmacology. These efforts are further enabled by functional genomic approaches that reveal gluable interfaces. Finally, the integration of chemical and biological data through machine learning is beginning to support rational de novo glue design.
AU - Gray,JL
AU - Xiao,Z
AU - Rogga,VV
AU - Zhang,X
AU - Tate,EW
DO - 10.1021/jacs.5c12299
EP - 4814
PY - 2026///
SP - 4791
TI - From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.
T2 - J Am Chem Soc
UR - http://dx.doi.org/10.1021/jacs.5c12299
UR - https://www.ncbi.nlm.nih.gov/pubmed/41622634
VL - 148
ER -
Prof. Ed Tate
GSK Chair in Chemical Biology
Department of Chemistry
Molecular Sciences Research Hub, White City Campus,
82 Wood Lane, London, W12 0BZ
e.tate@imperial.ac.uk
Tel: +44 (0)20 759 + ext 43752 or 45821