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Evolution of Cereblon-Mediated Protein Degradation as a Therapeutic Modality.

ABSTRACT: Many cellular processes and pathways are mediated by the regulation of protein-protein complexes. For example, E3 ubiquitin ligases recruit substrate proteins and transfer a ubiquitin tag to target those proteins for destruction by the proteasome. It has now been shown that this cellular process for protein destruction can be redirected by small molecules in both laboratory and clinical settings. This presents a new paradigm in drug discovery, enabling the rapid removal of target proteins linked to disease. In this Innovations review, we will describe the work done on cereblon as a case study on the different strategies available for targeted protein degradation.

SUBMITTER: Chamberlain PP

PROVIDER: S-EPMC6912861 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Evolution of Cereblon-Mediated Protein Degradation as a Therapeutic Modality.

Chamberlain Philip P PP D'Agostino Laura A LA Ellis J Michael JM Hansen Joshua D JD Matyskiela Mary E ME McDonald Joseph J JJ Riggs Jennifer R JR Hamann Lawrence G LG

ACS medicinal chemistry letters 20191112 12

Many cellular processes and pathways are mediated by the regulation of protein-protein complexes. For example, E3 ubiquitin ligases recruit substrate proteins and transfer a ubiquitin tag to target those proteins for destruction by the proteasome. It has now been shown that this cellular process for protein destruction can be redirected by small molecules in both laboratory and clinical settings. This presents a new paradigm in drug discovery, enabling the rapid removal of target proteins linked ...[more]

PMID: 31857833

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Ligand-mediated protein degradation reveals functional conservation among sequence variants of the CUL4-type E3 ligase substrate receptor cereblon.

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Continuous evolution of compact protein degradation tags regulated by selective cereblon molecular glues

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