A conjugated mTOR/MEK bifunctional inhibitor as potential polypharmacological anticancer agent: the prototype compound discovery
| العنوان: | A conjugated mTOR/MEK bifunctional inhibitor as potential polypharmacological anticancer agent: the prototype compound discovery |
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| المؤلفون: | Fang Fang, Can Zhao, Jingtai Liang, Qiangqiang Tao, Xiaodong Ma, Yong Wang, Hao Wang, Jiaming Li |
| المصدر: | Medicinal Chemistry Research |
| بيانات النشر: | Springer US, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | MAPK/ERK pathway, 010405 organic chemistry, Chemistry, Kinase, MEK inhibitor, Organic Chemistry, Allosteric regulation, Cross talk, 01 natural sciences, 0104 chemical sciences, mTOR/MEK bifunctional inhibitor, Allosteric MEK inhibitor, 010404 medicinal & biomolecular chemistry, chemistry.chemical_compound, Cell culture, Drug resistance, Cancer research, General Pharmacology, Toxicology and Pharmaceutics, Bifunctional, Protein kinase B, mTOR kinase inhibitor, PI3K/AKT/mTOR pathway, Original Research |
| الوصف: | mTOR/MEK bifunctional inhibitors have the potential to surmount the drug resistance aroused from cross talk between PI3K/Akt/mTOR (PAM) and Ras/MEK/ERK pathways. Herein, we report the discovery of a conjugated dual-targeted molecule, compound 13, as the prototype mTOR/MEK bifunctional inhibitor. It exhibited moderately high inhibitory activity against mTOR and MEK1 with IC50 values of 0.19 μM and 0.98 μM, respectively. In particular, it displayed attractive antiproliferative activity against both A549 (GI50 = 4.66 μM) and HCT116 (GI50 = 5.47 μM) cell lines. To our knowledge, it has been the first example of a conjugated mTOR/MEK bifunctional inhibitor. In addition, from this proof-of-principle study, it has become evident that the single-agent dual inhibition of mTOR and MEK can be fulfilled via covalently attaching mTOR kinase inhibitor to an allosteric MEK inhibitor. |
| اللغة: | English |
| تدمد: | 1554-8120 1054-2523 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fed8f77cc89d438c9b23d440854e7cde http://europepmc.org/articles/PMC7223898 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fed8f77cc89d438c9b23d440854e7cde |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15548120 10542523 |
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