دورية أكاديمية
Dual MET and SMO Negative Modulators Overcome Resistance to EGFR Inhibitors in Human Nonsmall Cell Lung Cancer
| العنوان: | Dual MET and SMO Negative Modulators Overcome Resistance to EGFR Inhibitors in Human Nonsmall Cell Lung Cancer |
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| المؤلفون: | Morgillo F., Amendola G., Della Corte C. M., Giacomelli C., Botta L., Di Maro S., Messere A., Ciaramella V., Taliani S., Marinelli L., Trincavelli M. L., Martini C., Novellino E., Ciardiello F., Cosconati S. |
| المساهمون: | Morgillo, F, Amendola, G, Della Corte, Cm, Giacomelli, C, Botta, L, Di Maro, S, Messere, A, Ciaramella, V, Taliani, S, Marinelli, L, Trincavelli, Ml, Martini, C, Novellino, E, Ciardiello, F, Cosconati, S |
| بيانات النشر: | AMER CHEMICAL SOC |
| سنة النشر: | 2017 |
| المجموعة: | Universitá degli Studi di Roma "Tor Vergata": ART - Archivio Istituzionale della Ricerca |
| مصطلحات موضوعية: | Animal, Antineoplastic Agent, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Cell Proliferation, Drug Repositioning, Drug Resistance, Neoplasm, ErbB Recexptor, Female, HEK293 Cell, Human, Lung, Lung Neoplasm, Mice, Inbred BALB C, Nude, Molecular Docking Simulation, Protein Kinase Inhibitor, Proto-Oncogene Proteins c-met, Smoothened Receptor, Settore CHIM/06 - CHIMICA ORGANICA |
| الوصف: | Tyrosine kinase inhibitors (TKIs) of the EGF receptor (EGFR) have provided a significant improvement in the disease outcome of nonsmall cell lung cancer (NSCLC). Unfortunately, resistance to these agents frequently occurs, and it is often related to the activation of the Hedgehog (Hh) and MET signaling cascades driving the epithelial-to-mesenchymal transition (EMT). Because the concomitant inhibition of both Hh and MET pathways restores the sensitivity to anti-EGFR drugs, here we aimed at discovering the first compounds that block simultaneously MET and SMO. By using an "in silico drug repurposing" approach and by validating our predictions both in vitro and in vivo, we identified a set of compounds with the desired dual inhibitory activity and enhanced antiproliferative activity on EGFR TKI-resistant NSCLC. The identification of the known MET TKIs, glesatinib and foretinib, as negative modulators of the Hh pathway, widens their application in the context of NSCLC. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/28787156; info:eu-repo/semantics/altIdentifier/wos/WOS:000411171700016; volume:60; issue:17; firstpage:7447; lastpage:7458; numberofpages:12; journal:JOURNAL OF MEDICINAL CHEMISTRY; http://hdl.handle.net/2108/273563Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85029542888 |
| DOI: | 10.1021/acs.jmedchem.7b00794 |
| الإتاحة: | https://doi.org/10.1021/acs.jmedchem.7b00794Test http://hdl.handle.net/2108/273563Test |
| رقم الانضمام: | edsbas.DDFAA796 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.7b00794 |
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