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Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 In Vivo.


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 |

REPOSITORIES: biostudies-literature

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