Browsing by author "Talbot, Rachel"
Now showing items 1-6 of 6
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Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders.
Bellenie, BR; Cheung, K-MJ; Varela, A; Pierrat, OA; Collie, GW; et al. (AMER CHEMICAL SOC, 2020-04-23)Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). ... -
Discovering cell-active BCL6 inhibitors: effectively combining biochemical HTS with multiple biophysical techniques, X-ray crystallography and cell-based assays.
Pierrat, OA; Liu, M; Collie, GW; Shetty, K; Rodrigues, MJ; et al. (NATURE PORTFOLIO, 2022-11-03)By suppressing gene transcription through the recruitment of corepressor proteins, B-cell lymphoma 6 (BCL6) protein controls a transcriptional network required for the formation and maintenance of B-cell germinal centres. ... -
Discovery of an In Vivo Chemical Probe for BCL6 Inhibition by Optimization of Tricyclic Quinolinones.
Harnden, AC; Davis, OA; Box, GM; Hayes, A; Johnson, LD; et al. (AMER CHEMICAL SOC, 2023-04-27)B-cell lymphoma 6 (BCL6) is a transcriptional repressor and oncogenic driver of diffuse large B-cell lymphoma (DLBCL). Here, we report the optimization of our previously reported tricyclic quinolinone series for the ... -
Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 In Vivo.
Huckvale, R; Harnden, AC; Cheung, K-MJ; Pierrat, OA; Talbot, R; et al. (AMER CHEMICAL SOC, 2022-06-23)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 ... -
Into Deep Water: Optimizing BCL6 Inhibitors by Growing into a Solvated Pocket.
Lloyd, MG; Huckvale, R; Cheung, K-MJ; Rodrigues, MJ; Collie, GW; et al. (AMER CHEMICAL SOC, 2021-12-09)We describe the optimization of modestly active starting points to potent inhibitors of BCL6 by growing into a subpocket, which was occupied by a network of five stably bound water molecules. Identifying potent inhibitors ... -
Optimizing Shape Complementarity Enables the Discovery of Potent Tricyclic BCL6 Inhibitors.
Davis, OA; Cheung, K-MJ; Brennan, A; Lloyd, MG; Rodrigues, MJ; et al. (AMER CHEMICAL SOC, 2022-06-23)To identify new chemical series with enhanced binding affinity to the BTB domain of B-cell lymphoma 6 protein, we targeted a subpocket adjacent to Val18. With no opportunities for strong polar interactions, we focused on ...