Protein Degradation with New Chemical Modalities
Chapter 5: New Activities of CELMoDs, Cereblon E3 Ligase-modulating Drugs
Published:07 Oct 2020
M. E. Matyskiela, T. Clayton, J. W. Thompson, C. Carroll, L. Bateman, L. LeBrun, and P. P. Chamberlain, in Protein Degradation with New Chemical Modalities, ed. H. Weinmann and C. Crews, The Royal Society of Chemistry, 2020, ch. 5, pp. 94-114.
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CELMoDs (cereblon E3 ligase-modulating drugs) are low-molecular-weight small molecules that induce the recruitment of specific protein targets to the cereblon-CRL4 ubiquitin ligase for ubiquitination and subsequent cellular degradation. CELMoDs act to scaffold direct protein–protein interactions between cereblon and substrate, working through a so-called “molecular glue” mechanism. We discuss recent discoveries in CELMoD mechanism of action, including approaches taken to expand the scope of cereblon neosubstrates, and discuss the future and breadth of this emerging class of molecules.