Discovery of SIPI6473, a New, Potent, and Orally Bioavailable Multikinase Inhibitor for the Treatment of Non-small Cell Lung Cancer
Abstract A novel series of quinazoline derivatives were designed, synthesized, and evaluated as multikinase inhibitors. Most of these compounds showed antiproliferation activities of several human cancer cell lines and exhibited inhibition efficacy against the estimated glomerular filtration rate (E...
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| Format: | Article |
| Language: | English |
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Georg Thieme Verlag KG
2021-03-01
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| Series: | Pharmaceutical Fronts |
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| Online Access: | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0041-1731081 |
| _version_ | 1818441045332983808 |
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| author | Xiu Gu Zi-Xue Zhang Min-Ru Jiao Xin-Yan Peng Jian-Qi Li Qing-Wei Zhang |
| author_facet | Xiu Gu Zi-Xue Zhang Min-Ru Jiao Xin-Yan Peng Jian-Qi Li Qing-Wei Zhang |
| author_sort | Xiu Gu |
| collection | DOAJ |
| description | Abstract
A novel series of quinazoline derivatives were designed, synthesized, and evaluated as multikinase inhibitors. Most of these compounds showed antiproliferation activities of several human cancer cell lines and exhibited inhibition efficacy against the estimated glomerular filtration rate (EGFR) in the nanomolar level. Among those compounds, compound B5 (also named SIPI6473) displayed the maximum effect, and thus was chosen for further study. Our data revealed that B5 inhibited the activity of several kinases (such as EGFR, VEGFR2, and PDGFRα) that contributed to the development of non-small cell lung cancer (NSCLC). Besides, an in vivo study also showed that B5 inhibited tumor growth without signs of adverse effects in the A549 xenograft model. In conclusion, B5 may represent a new and promising drug for the treatment of NSCLC. |
| first_indexed | 2024-12-14T18:22:00Z |
| format | Article |
| id | doaj.art-eaefe007f52e4ce596062c959176ea2e |
| institution | Directory Open Access Journal |
| issn | 2628-5088 2628-5096 |
| language | English |
| last_indexed | 2024-12-14T18:22:00Z |
| publishDate | 2021-03-01 |
| publisher | Georg Thieme Verlag KG |
| record_format | Article |
| series | Pharmaceutical Fronts |
| spelling | doaj.art-eaefe007f52e4ce596062c959176ea2e2022-12-21T22:52:03ZengGeorg Thieme Verlag KGPharmaceutical Fronts2628-50882628-50962021-03-010301e1e710.1055/s-0041-1731081Discovery of SIPI6473, a New, Potent, and Orally Bioavailable Multikinase Inhibitor for the Treatment of Non-small Cell Lung CancerXiu Gu0Zi-Xue Zhang1Min-Ru Jiao2Xin-Yan Peng3Jian-Qi Li4Qing-Wei Zhang5Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of ChinaNovel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of ChinaNovel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of ChinaNovel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of ChinaNovel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of ChinaNovel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of ChinaAbstract A novel series of quinazoline derivatives were designed, synthesized, and evaluated as multikinase inhibitors. Most of these compounds showed antiproliferation activities of several human cancer cell lines and exhibited inhibition efficacy against the estimated glomerular filtration rate (EGFR) in the nanomolar level. Among those compounds, compound B5 (also named SIPI6473) displayed the maximum effect, and thus was chosen for further study. Our data revealed that B5 inhibited the activity of several kinases (such as EGFR, VEGFR2, and PDGFRα) that contributed to the development of non-small cell lung cancer (NSCLC). Besides, an in vivo study also showed that B5 inhibited tumor growth without signs of adverse effects in the A549 xenograft model. In conclusion, B5 may represent a new and promising drug for the treatment of NSCLC.http://www.thieme-connect.de/DOI/DOI?10.1055/s-0041-1731081sipi6473multikinase inhibitorantitumornon-small cell lung cancer |
| spellingShingle | Xiu Gu Zi-Xue Zhang Min-Ru Jiao Xin-Yan Peng Jian-Qi Li Qing-Wei Zhang Discovery of SIPI6473, a New, Potent, and Orally Bioavailable Multikinase Inhibitor for the Treatment of Non-small Cell Lung Cancer Pharmaceutical Fronts sipi6473 multikinase inhibitor antitumor non-small cell lung cancer |
| title | Discovery of SIPI6473, a New, Potent, and Orally Bioavailable Multikinase Inhibitor for the Treatment of Non-small Cell Lung Cancer |
| title_full | Discovery of SIPI6473, a New, Potent, and Orally Bioavailable Multikinase Inhibitor for the Treatment of Non-small Cell Lung Cancer |
| title_fullStr | Discovery of SIPI6473, a New, Potent, and Orally Bioavailable Multikinase Inhibitor for the Treatment of Non-small Cell Lung Cancer |
| title_full_unstemmed | Discovery of SIPI6473, a New, Potent, and Orally Bioavailable Multikinase Inhibitor for the Treatment of Non-small Cell Lung Cancer |
| title_short | Discovery of SIPI6473, a New, Potent, and Orally Bioavailable Multikinase Inhibitor for the Treatment of Non-small Cell Lung Cancer |
| title_sort | discovery of sipi6473 a new potent and orally bioavailable multikinase inhibitor for the treatment of non small cell lung cancer |
| topic | sipi6473 multikinase inhibitor antitumor non-small cell lung cancer |
| url | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0041-1731081 |
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