التفاصيل البيبلوغرافية
| العنوان: |
Design, Synthesis, and Biological Evaluation of Novel EGFR PROTACs Targeting Del19/T790M/C797S Mutation |
| المؤلفون: |
Hualin Zhang (11948553), Ruliang Xie (11948556), Hawaa AI-furas (11948559), Yupeng Li (507508), Qingxia Wu (11948562), Jian Li (41607), Fang Xu (138747), Tianfeng Xu (1884211) |
| سنة النشر: |
2022 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Microbiology, Cell Biology, Genetics, Molecular Biology, Pharmacology, Biotechnology, Developmental Biology, Cancer, Infectious Diseases, Virology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, develop therapeutic agents, acquired mutational resistance, one representative compound, molecule inhibitors targeting, generation egfr inhibitors, c797s mutation predominates, 6h , 50 , egfr c797s mutants, egfr c797s mutation, c797s triple mutant, c797s , f3 cells expressing, c797s mutation, targeting chimeras, lead compound |
| الوصف: |
The tertiary epidermal growth factor receptor (EGFR) C797S mutation predominates in the acquired mutational resistance in cancer patients to third-generation EGFR inhibitors. Small-molecule inhibitors targeting the EGFR C797S mutation have been developed with good efficiency. However, these compounds may still induce new EGFR mutations to evade the inhibition pathway. One EGFR protein degrader based on an allosteric inhibitor has shown some benefits of degrading the EGFR L858R/T790M/C797S triple mutant. However, the degrader of the other important triple EGFR mutation Del19/T790M/C797S has not been reported. Here we present the design and synthesis of a series of EGFR proteolysis-targeting chimeras (PROTACs) that can rapidly and potently induce EGFR degradation in Ba/F3 cells expressing the EGFR Del19/T790M/C797S mutant. One representative compound 6h time- and dose-dependently induced EGFR degradation with a DC 50 of 8 nM. It also showed good antiproliferation activity (IC 50 = 0.02 μM) against Ba/F3-EGFR Del19/T790M/C797S cells. 6h may serve as a lead compound to develop therapeutic agents for the treatment of resistant non-small cell lung cancer patients with EGFR C797S mutants. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/journal_contribution/Design_Synthesis_and_Biological_Evaluation_of_Novel_EGFR_PROTACs_Targeting_Del19_T790M_C797S_Mutation/18410262Test |
| DOI: |
10.1021/acsmedchemlett.1c00645.s001 |
| الإتاحة: |
https://doi.org/10.1021/acsmedchemlett.1c00645.s001Test |
| حقوق: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.82DEB543 |
| قاعدة البيانات: |
BASE |
