Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 <i>In Vivo</i>.

ABSTRACT: The transcriptional repressor BCL6 is an oncogenic driver found to be deregulated in lymphoid malignancies. Herein, we report the optimization of our previously reported benzimidazolone molecular glue-type degrader CCT369260 to CCT373566, a highly potent probe suitable for sustained depletion of BCL6 in vivo. We observed a sharp degradation SAR, where subtle structural changes conveyed the ability to induce degradation of BCL6. CCT373566 showed modest in vivo efficacy in a lymphoma xenograft mouse model following oral dosing.

SUBMITTER: Huckvale R 

PROVIDER: S-EPMC9234961 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature