Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 .

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 to , a highly potent probe suitable for sustained depletion of BCL6 . We observed a sharp degradation SAR, where subtle structural changes conveyed the ability to induce degradation of BCL6. showed modest efficacy in a lymphoma xenograft mouse model following oral dosing.