دورية أكاديمية
Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 In Vivo.
| العنوان: | Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 In Vivo. |
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| المؤلفون: | Huckvale, R, Harnden, AC, Cheung, K-MJ, Pierrat, OA, Talbot, R, Box, GM, Henley, AT, de Haven Brandon, AK, Hallsworth, AE, Bright, MD, Akpinar, HA, Miller, DSJ, Tarantino, D, Gowan, S, Hayes, A, Gunnell, EA, Brennan, A, Davis, OA, Johnson, LD, de Klerk, S, McAndrew, C, Le Bihan, Y-V, Meniconi, M, Burke, R, Kirkin, V, van Montfort, RLM, Raynaud, FI, Rossanese, OW, Bellenie, BR, Hoelder, S |
| المساهمون: | Pierrat, Olivier, Talbot, Rachel, Gowan, Sharon, Burke, Rosemary, Van Montfort, Robert, Raynaud, Florence, Rossanese, Olivia, Hoelder, Swen |
| بيانات النشر: | AMER CHEMICAL SOC |
| سنة النشر: | 2022 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | Animals, Carcinogenesis, Gene Expression Regulation, Neoplastic, Humans, Mice, Proto-Oncogene Proteins c-bcl-6 |
| جغرافية الموضوع: | United States |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; 8207; application/pdf |
| اللغة: | English |
| تدمد: | 0022-2623 1520-4804 |
| العلاقة: | Journal of Medicinal Chemistry, 2022, 65 (12), pp. 8191 - 8207; https://repository.icr.ac.uk/handle/internal/5312Test |
| DOI: | 10.1021/acs.jmedchem.1c02175 |
| الإتاحة: | https://doi.org/10.1021/acs.jmedchem.1c02175Test https://repository.icr.ac.uk/handle/internal/5312Test |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.CE75200B |
| قاعدة البيانات: | BASE |
| تدمد: | 00222623 15204804 |
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| DOI: | 10.1021/acs.jmedchem.1c02175 |