Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790M
A new class of EGFR PROTACs based on pomalidomide was developed, synthesised, and tested for their cytotoxic activity against a panel of human cancer cells. Compounds 15–21 were showed to be more effective against the four tested cell lines than erlotinib. In particular, compound 16 was found to be...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2062338 |
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| _version_ | 1849687510105456640 |
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| author | Moustafa O. Aboelez Amany Belal Guangya Xiang Xiang Ma |
| author_facet | Moustafa O. Aboelez Amany Belal Guangya Xiang Xiang Ma |
| author_sort | Moustafa O. Aboelez |
| collection | DOAJ |
| description | A new class of EGFR PROTACs based on pomalidomide was developed, synthesised, and tested for their cytotoxic activity against a panel of human cancer cells. Compounds 15–21 were showed to be more effective against the four tested cell lines than erlotinib. In particular, compound 16 was found to be the most potent counterpart as it was 5.55, 4.34, 5.04, and 7.18 times more active than erlotinib against MCF-7, HepG-2, HCT-116, and A549 cells, respectively. Compound 15 was revealed to be more active than doxorubicin against the four tested cell lines. Furthermore, the most potent cytotoxic compounds were studied further for their kinase inhibitory effects against EGFRWT and EGFRT790M using HTRF test. Compound 16 showed to be the most effective against both kinds of EGFR, with IC50 values of 0.10 and 4.02 µM, respectively. Compound 16 could effectively degrade EGFR protein through ubiquitination (Dmax = 96%) at 72 h in the tested cells. |
| format | Article |
| id | doaj-art-1c3f97a53c4346b0a6eb670ff23cc4e2 |
| institution | DOAJ |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-1c3f97a53c4346b0a6eb670ff23cc4e22025-08-20T03:22:19ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013711196121110.1080/14756366.2022.2062338Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790MMoustafa O. Aboelez0Amany Belal1Guangya Xiang2Xiang Ma3School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif, Saudi ArabiaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaA new class of EGFR PROTACs based on pomalidomide was developed, synthesised, and tested for their cytotoxic activity against a panel of human cancer cells. Compounds 15–21 were showed to be more effective against the four tested cell lines than erlotinib. In particular, compound 16 was found to be the most potent counterpart as it was 5.55, 4.34, 5.04, and 7.18 times more active than erlotinib against MCF-7, HepG-2, HCT-116, and A549 cells, respectively. Compound 15 was revealed to be more active than doxorubicin against the four tested cell lines. Furthermore, the most potent cytotoxic compounds were studied further for their kinase inhibitory effects against EGFRWT and EGFRT790M using HTRF test. Compound 16 showed to be the most effective against both kinds of EGFR, with IC50 values of 0.10 and 4.02 µM, respectively. Compound 16 could effectively degrade EGFR protein through ubiquitination (Dmax = 96%) at 72 h in the tested cells.https://www.tandfonline.com/doi/10.1080/14756366.2022.2062338EGFRPROTACspomalidomideapoptosis inductionanticancer agents |
| spellingShingle | Moustafa O. Aboelez Amany Belal Guangya Xiang Xiang Ma Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790M Journal of Enzyme Inhibition and Medicinal Chemistry EGFR PROTACs pomalidomide apoptosis induction anticancer agents |
| title | Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790M |
| title_full | Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790M |
| title_fullStr | Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790M |
| title_full_unstemmed | Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790M |
| title_short | Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790M |
| title_sort | design synthesis and molecular docking studies of novel pomalidomide based protacs as potential anti cancer agents targeting egfrwt and egfrt790m |
| topic | EGFR PROTACs pomalidomide apoptosis induction anticancer agents |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2062338 |
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