Molecular Glue Technology Development

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Consult with Our Experts

As a leading CRO, BOC Sciences has been working in the field of targeted protein degradation for over a decade. In addition to our established PROTAC technology platform, we also have expertise in the field of molecular glue. Molecular glue, one of the major targeted protein degraders, mediates the binding of E3 ubiquitin ligases to the target protein and leads to protein degradation. With our experienced team of experts, we are able to provide molecular glue service to assist our customers in their research and development.

Introduction

Molecular glues are small molecules that induce protein-protein associations and allow precise control of various biological processes, such as signal transduction, transcription, chromatin regulation, protein folding, localization, and degradation. 'Molecular glue' is a term coined and later used to describe synthetic small molecule protein degraders, such as immunomodulatory imide drugs (IMiD, e.g., thalidomide, lenalidomide), whose mechanism of action is different from PROTAC.

Molecular glue has no affinity for target proteins, but it can bind to E3 ubiquitin ligases and contact the target protein with their help, thereby mediating and enhancing the interaction between target proteins and E3 ligases. This property allows molecular glue to degrade 'undruggable' targets that do not have small molecule binding pockets through the protease system. Unlike molecular glue, PROTAC is designed to start with a ligand that binds to the target protein and therefore cannot act on target proteins that do not have pockets.

Molecular Glue Technology

Protein-protein interactions mediate various biological functions and are regulated by molecular glues. As chemical inducers of proximity, molecular glues promote the dimerization or co-localization of two proteins by forming ternary complexes, resulting in different biological potencies. Members of molecular glues include natural products and modified or synthetic molecular glues.

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References

  1. Cao, S., Kang, S., Mao, H., Yao, J., Gu, L., and Zheng, N., Defining molecular glues with a dual-nanobody cannabidiol sensor, Nat. Commun., 2022, 13, 815.
  2. Dong, G., Ding, Y., He, S., and Sheng, C., Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery, J. Med. Chem., 2021, 64, 15, 10606-10620.
  3. Schreiber, S. L., The Rise of Molecular Glues, benchmarks, 2021, 184, 3-9.
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