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Updated: Sep 21, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 In Vivo
Rosemary Huckvale1, Alice C Harnden1, Kwai-Ming J Cheung1
1Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K.
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.
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