Homolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML.

ABSTRACT: The design of selective small molecules is often stymied by similar ligand binding pockets. Here, we report BSJ-03-123, a phthalimide-based degrader that exploits protein-interface determinants to achieve proteome-wide selectivity for the degradation of cyclin-dependent kinase 6 (CDK6). Pharmacologic CDK6 degradation targets a selective dependency of acute myeloid leukemia cells, and transcriptomics and phosphoproteomics profiling of acute degradation of CDK6 enabled dynamic mapping of its immediate role in coordinating signaling and transcription.

SUBMITTER: Brand M 

PROVIDER: S-EPMC6444916 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature