| Literature DB >> 35653645 |
Rosemary Huckvale1, Alice C Harnden1, Kwai-Ming J Cheung1, Olivier A Pierrat1, Rachel Talbot1, Gary M Box1, Alan T Henley1, Alexis K de Haven Brandon1, Albert E Hallsworth1, Michael D Bright1, Hafize Aysin Akpinar1, Daniel S J Miller1, Dalia Tarantino1, Sharon Gowan1, Angela Hayes1, Emma A Gunnell1,2, Alfie Brennan1, Owen A Davis1, Louise D Johnson1, Selby de Klerk1, Craig McAndrew1, Yann-Vaï Le Bihan1,2, Mirco Meniconi1, Rosemary Burke1, Vladimir Kirkin1, Rob L M van Montfort1,2, Florence I Raynaud1, Olivia W Rossanese1, Benjamin R Bellenie1, Swen Hoelder1.
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.Entities:
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Year: 2022 PMID： 35653645 PMCID： PMC9234961 DOI： 10.1021/acs.jmedchem.1c02175
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 8.039