Molecular Glues & Bifunctional Compounds: 
Therapeutic Modalities Based on Induced Proximity

Stuart Schreiber

doi:10.26434/chemrxiv-2024-q1n61-v2

Biological and Medicinal Chemistry

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Molecular Glues & Bifunctional Compounds: Therapeutic Modalities Based on Induced Proximity

03 April 2024, Version 2

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Stuart Schreiber

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This content is a preprint and has not undergone peer review at the time of posting.

Abstract

This Perspective explores molecular glues and bifunctional compounds – proximity-inducing compounds – and offers a framework to understand and exploit their similarity to hot spots, missense mutations, and posttranslational modifications (PTMs).

Keywords

Molecular Glues

Chemical inducers of proximity

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Version History

Apr 03, 2024 Version 2

Apr 01, 2024 Version 1

Version Notes

Updates to figures: Figure 1E: Removed open black circles. Added "human" to the label in the bottom center Added label "cereblon + lenalidomide" in the bottom right corner. Slightly modified cartoon proteins to be consistent with earlier representations. Figure 4B: Removed stray line from under left-most DNA structure. Figure 4C: Changed bar graph color from grey to blue. Figure 5B: Returned displaced orange shapes in the bottom two panels to their binding sites. Figure 5D: Bolded the text, "molecular glue"

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License

The content is available under CC BY NC ND 4.0

DOI

10.26434/chemrxiv-2024-q1n61-v2

Author’s competing interest statement

S.L.S. is a shareholder and advises Magnet Biomedicine and is the Founding C.E.O. of Arena BioWorks, LLC.

Ethics

The author(s) have declared ethics committee/IRB approval is not relevant to this content