Small-molecule-induced polymerization triggers degradation of BCL6.

ABSTRACT: Effective and sustained inhibition of non-enzymatic oncogenic driver proteins is a major pharmacological challenge. The clinical success of thalidomide analogues demonstrates the therapeutic efficacy of drug-induced degradation of transcription factors and other cancer targets^1-3, but a substantial subset of proteins are resistant to targeted degradation using existing approaches^4,5. Here we report an alternative mechanism of targeted protein degradation, in which a small molecule induces the highly specific, reversible polymerization of a target protein, followed by its sequestration into cellular foci and subsequent degradation. BI-3802 is a small molecule that binds to the Broad-complex, Tramtrack and Bric-à-brac (BTB) domain of the oncogenic transcription factor B

SUBMITTER: Slabicki M 

PROVIDER: S-EPMC7816212 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature