دورية أكاديمية
Structure-activity exploration of a small-molecule allosteric inhibitor of T790M/L858R double mutant EGFR
| العنوان: | Structure-activity exploration of a small-molecule allosteric inhibitor of T790M/L858R double mutant EGFR |
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| المؤلفون: | Francesca Foschi, Annachiara Tinivella, Valentina Crippa, Luca Pinzi, Luca Mologni, Daniele Passarella, Giulio Rastelli |
| المصدر: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 38, Iss 1, Pp 239-245 (2023) |
| بيانات النشر: | Taylor & Francis Group, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | EGFR inhibitors, allosteric inhibitors, anticancer drugs, drug design, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | AbstractEGFR is a protein kinase whose aberrant activity is frequently involved in the development of non-small lung cancer (NSCLC) drug resistant forms. The allosteric inhibition of this enzyme is currently one among the most attractive approaches to design and develop anticancer drugs. In a previous study, we reported the identification of a hit compound acting as type III allosteric inhibitor of the L858R/T790M double mutant EGFR. Herein, we report the design, synthesis and in vitro testing of a series of analogues of the previously identified hit with the aim of exploring the structure-activity relationships (SAR) around this scaffold. The performed analyses allowed us to identify two compounds 15 and 18 showing improved inhibition of double mutant EGFR with respect to the original hit, as well as interesting antiproliferative activity against H1975 NSCLC cancer cells expressing double mutant EGFR. The newly discovered compounds represent promising starting points for further hit-to-lead optimisation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 14756366 1475-6374 1475-6366 |
| العلاقة: | https://doaj.org/toc/1475-6366Test; https://doaj.org/toc/1475-6374Test |
| DOI: | 10.1080/14756366.2022.2145284 |
| الوصول الحر: | https://doaj.org/article/25d2bf8ec18e40be90168dfa859cc71cTest |
| رقم الانضمام: | edsdoj.25d2bf8ec18e40be90168dfa859cc71c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14756366 14756374 |
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| DOI: | 10.1080/14756366.2022.2145284 |