Developing MYC Degraders Bearing the Von Hippel-Lindau Ligand to Target the "Undruggable" MYC.

ABSTRACT: Although small-molecule inhibitors with moderate efficacy targeting MYC have been previously described, to this point, research efforts have failed to bring a suitable small-molecule MYC inhibitor to the clinic. Herein, the discovery of a series of novel MYC degraders bearing VHL to target the "undruggable" MYC is presented. The molecules are based on connecting a known MYC binder to a VHL ligand or pomalidomide to induce MYC degradation in various cancer cells known to express MYC. Representative compounds from our work induced MYC degradation in a time- and dose-dependent manner. Selected compounds, CSI86 and CSI107, displayed antiproliferative activity (IC₅₀ values of 13-18 μM) against breast and prostate cancer cells. The lead molecules were further evaluated i

SUBMITTER: Siokatas C 

PROVIDER: S-EPMC11650737 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature