التفاصيل البيبلوغرافية
| العنوان: |
Gut-Restricted Selective Cyclooxygenase‑2 (COX-2) Inhibitors for Chemoprevention of Colorectal Cancer |
| المؤلفون: |
Zhuming Zhang (1846087), Avijit Ghosh (1428496), Peter J. Connolly (2456890), Peter King (234747), Thomas Wilde (6057116), Jianyao Wang (640348), Yawei Dong (2365990), Xueliang Li (585599), Daohong Liao (1393399), Hao Chen (5190), Gaochao Tian (2465608), Javier Suarez (2289811), William G. Bonnette (11173075), Vineet Pande (2538973), Karen A. Diloreto (11154645), Yifan Shi (4269262), Shefali Patel (11154648), Beth Pietrak (1940869), Lawrence Szewczuk (11154651), Carlo Sensenhauser (2181964), Shannon Dallas (7945637), James P. Edwards (2428411), Kurtis E. Bachman (5679542), David C. Evans (203487) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Physiology, Pharmacology, Biotechnology, Cancer, Infectious Diseases, Space Science, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, adenoma progression, Colorectal Cancer, vivo 18 F-FDG uptake attenuation, efficacy proxy, survival extension, COX -2 inhibitors, COX -2-mediated CRC disease chemopr., colorectal adenomas, APC, exposure, chemoprotective effects, COX -2 inhibition, vivo dose-dependent inhibition |
| الوصف: |
Selective cyclooxygenase (COX)-2 inhibitors have been extensively studied for colorectal cancer (CRC) chemoprevention. Celecoxib has been reported to reduce the incidence of colorectal adenomas and CRC but is also associated with an increased risk of cardiovascular events. Here, we report a series of gut-restricted, selective COX-2 inhibitors characterized by high colonic exposure and minimized systemic exposure. By establishing acute ex vivo 18 F-FDG uptake attenuation as an efficacy proxy, we identified a subset of analogues that demonstrated statistically significant in vivo dose-dependent inhibition of adenoma progression and survival extension in an APC min/+ mouse model. However, in vitro–in vivo correlation analysis showed their chemoprotective effects were driven by residual systemic COX-2 inhibition, rationalizing their less than expected efficacies and highlighting the challenges associated with COX-2-mediated CRC disease chemoprevention. |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/Gut-Restricted_Selective_Cyclooxygenase_2_COX-2_Inhibitors_for_Chemoprevention_of_Colorectal_Cancer/15019020 |
| DOI: |
10.1021/acs.jmedchem.1c00890.s001 |
| الاتاحة: |
https://doi.org/10.1021/acs.jmedchem.1c00890.s001 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.8C76A959 |
| قاعدة البيانات: |
BASE |