作者
Rosemary Huckvale,Alice C. Harnden,Kwai-Ming J. Cheung,Olivier A. Pierrat,Rachel Talbot,Gary Box,Alan T. Henley,Alexis K. de Haven Brandon,Albert Hallsworth,Michael D. Bright,Hafize Aysin Akpinar,Daniel S. J. Miller,Dalia Tarantino,Sharon Gowan,Angela Hayes,Emma A. Gunnell,Alfie Brennan,Owen A. Davis,Linda Y Johnson,Selby de Klerk,Craig McAndrew,Yann‐Vaï Le Bihan,Mirco Meniconi,Rosemary Burke,Vladimir Kirkin,R.L.M. van Montfort,Florence I. Raynaud,Olivia W. Rossanese,Benjamin R. Bellenie,Swen Hoelder
摘要
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.