The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K.

ABSTRACT: Molecular glue compounds induce protein-protein interactions that, in the context of a ubiquitin ligase, lead to protein degradation¹. Unlike traditional enzyme inhibitors, these molecular glue degraders act substoichiometrically to catalyse the rapid depletion of previously inaccessible targets². They are clinically effective and highly sought-after, but have thus far only been discovered serendipitously. Here, through systematically mining databases for correlations between the cytotoxicity of 4,518 clinical and preclinical small molecules and the expression levels of E3 ligase components across hundreds of human cancer cell lines^3-5, we identify CR8-a cyclin-dependent kinase (CDK) inhibitor⁶-as a compound that acts as a molecular glue degrader

SUBMITTER: Slabicki M 

PROVIDER: S-EPMC7486275 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature