From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology
Abstract
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.
Fields of Study & Subjects
Click Chemistry and Applications
Chemical Synthesis and Analysis
Protein Degradation and Inhibitors
Publication details
- Journal / source
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Volume
- 148
- Issue
- 5
- Pages
- 4791–4814
- Publication date
- 2 February 2026
- Language
- EN