التفاصيل البيبلوغرافية
| العنوان: |
Discovery of 3,4-Dihydrobenzo[ f ][1,4]oxazepin-5(2 H )‑one Derivatives as a New Class of Selective TNIK Inhibitors and Evaluation of Their Anti-Colorectal Cancer Effects |
| المؤلفون: |
Yueshan Li (2106667), Liting Zhang (2883890), Ruicheng Yang (6188681), Zeen Qiao (6066263), Ming Wu (238132), Chong Huang (799290), Chenyu Tian (7900979), Xinling Luo (11910086), Wei Yang (109917), Yun Zhang (131894), Linli Li (436139), Shengyong Yang (2123410) |
| سنة النشر: |
2022 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Cell Biology, Pharmacology, Immunology, Cancer, Infectious Diseases, Virology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Information Systems not elsewhere classified, interacting protein kinase, downstream signal protein, 026 ± 0, 008 μm ), >)‑ one derivatives, >)- one derivatives, promising lead compound, colorectal cancer effects, catenin signaling pathway, selective tnik inhibitors, potent tnik inhibitors, 21k , 5 ( 2, 4 ] oxazepin, colorectal cancer, catenin pathway, tnik inhibitors, active one, vitro <, h < |
| الوصف: |
The Traf2- and Nck-interacting protein kinase (TNIK) is a downstream signal protein of the Wnt/β-catenin pathway and has been thought of as a potential target for the treatment of colorectal cancer (CRC) that is often associated with dysregulation of Wnt/β-catenin signaling pathway. Herein, we report the discovery of a series of 3,4-dihydrobenzo[ f ][1,4]oxazepin-5(2 H )-one derivatives as a new class of TNIK inhibitors. Structure–activity relationship (SAR) analyses led to the identification of a number of potent TNIK inhibitors with compound 21k being the most active one (IC 50 : 0.026 ± 0.008 μM). This compound also displayed excellent selectivity for TNIK against 406 other kinases. Compound 21k could efficiently suppress CRC cell proliferation and migration in in vitro assays and exhibited considerable antitumor activity in the HCT116 xenograft mouse model. It also showed favorable pharmacokinetic properties. Overall, 21k could be a promising lead compound for drug discovery targeting TNIK and deserves further studies. |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/Discovery_of_3_4-Dihydrobenzo_i_f_i_1_4_oxazepin-5_2_i_H_i_one_Derivatives_as_a_New_Class_of_Selective_TNIK_Inhibitors_and_Evaluation_of_Their_Anti-Colorectal_Cancer_Effects/17909693 |
| DOI: |
10.1021/acs.jmedchem.1c00672.s004 |
| الاتاحة: |
https://doi.org/10.1021/acs.jmedchem.1c00672.s004 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.7FF634CB |
| قاعدة البيانات: |
BASE |