| Autor: |
Xin-Yang, Li, Xin-Hua, Qian, Ju, Zhu, Yu-Heng, Li, Qi-Qi, Lin, Shuai, Li, Wen-Han, Xue, Ling-Yan, Jian, Fan-Hao, Meng |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
European Journal of Medicinal Chemistry. 237:114325 |
| ISSN: |
0223-5234 |
| Popis: |
Human epidermal growth factor receptor 2 (HER-2) is an essential member of the receptor tyrosine kinase (RTK) superfamily and has been reported as a critical method for treating HER-2 positive breast cancer. Here, we retained (E)-4-methyl-2-(4-(trifluoromethyl)styryl)oxazole, a fragment of HER-2 inhibitor Mubritinib, and synthesized 32 novel compounds from it. We screened out the most potential compound Q7j with HER-2 positive breast cancer cells through MTT assays, which possessed low toxicity on normal cells (MCF7-10A). Subsequently, wound healing, transwell, western blotting, and immunofluorescence experiments were performed, and it was found that compound Q7j could suppress cell migration by inhibiting the phosphorylation of HER-2 and affecting the expression of EMT-related proteins. Moreover, the SKBR3 orthotopic xenograft model confirmed that compound Q7j was more effective than Mubritinib in inhibiting the proliferation of cancer cells. In general, compound Q7j was a potential HER-2 inhibitor in treating breast cancer, which may be of great significance for developing and improving HER-2 small molecule inhibitors. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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