The DOI matches its Crossref record; 74 of the 76 references it cites were found in a registry or an index.
Molecular glues and bifunctional compounds: Therapeutic modalities based on induced proximity
Open accessPublished version of a preprint
Abstract
This Perspective explores molecular glues and bifunctional compounds-proximity-inducing compounds-and offers a framework to understand and exploit their similarity to hotspots, missense mutations, and posttranslational modifications (PTMs). This view is also shown to be relevant to intramolecular glues, where compounds induce contacts between distinct domains of the same protein. A historical perspective of these compounds is presented that shows the field has come full circle from molecular glues targeting native proteins, to bifunctionals targeting fusion proteins, and back to molecular glues and bifunctionals targeting native proteins. Modern screening methods and data analyses with pre-selected target proteins are shown to yield either cooperative molecular glues or bifunctional compounds that induce proximity, thereby enabling novel functional outcomes.
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“Taken together, our findings provide another example that the underlying principles of molecular glue mechanisms might be rooted in the partial mimicry of naturally occurring PPIs at preexisting sites of high PPI propensity, interactions that are further enhanced by a matching molecular glue1,10,11,50–54.”
From Cereblon induces G3BP2 neosubstrate degradation using molecular surface mimicry (2026) · cites this paper as [1]
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Metadata
- Authors
- Schreiber, S. L.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Schreiber, Stuart L.
- ORCID
- Schreiber, Stuart L.
- Venue
- Cell Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2024-06
- Volume
- 31
- Issue
- 6
- Pages
- 1050-1063
- ISSN
- 2451-9448 (ISSN-L)
- 2451-9456
- OpenAlex
- W4399491693
- Semantic Scholar
- bdf154bc8ee372bd5acec4d6a1562bb429223611
- Cited by
- 112
- References
- 76
- Citations by year
- 2026: 41 · 2025: 62 · 2024: 9
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell chemical biology (publishedVersion, cc-by-nc-nd)
- ChemRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Keywords
- molecular glues, bifunctional molecules, induced proximity, protein-protein interaction, fusion protein, missense mutations, post-translational modification, drug screening
- MeSH terms
- Humans, Protein Processing, Post-Translational, Proteins, Mutation, Missense
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