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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Main Authors:	Xiu Gu, Zi-Xue Zhang, Min-Ru Jiao, Xin-Yan Peng, Jian-Qi Li, Qing-Wei Zhang
Format:	Article
Language:	English
Published:	Georg Thieme Verlag KG 2021-03-01
Series:	Pharmaceutical Fronts
Subjects:	sipi6473 multikinase inhibitor antitumor non-small cell lung cancer
Online Access:	http://www.thieme-connect.de/DOI/DOI?10.1055/s-0041-1731081

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spelling	doaj-eaefe007f52e4ce596062c959176ea2e2021-06-23T22:30:32ZengGeorg 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
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Xiu Gu Zi-Xue Zhang Min-Ru Jiao Xin-Yan Peng Jian-Qi Li Qing-Wei Zhang
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
author_facet	Xiu Gu Zi-Xue Zhang Min-Ru Jiao Xin-Yan Peng Jian-Qi Li Qing-Wei Zhang
author_sort	Xiu Gu
title	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_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_sort	discovery of sipi6473, a new, potent, and orally bioavailable multikinase inhibitor for the treatment of non-small cell lung cancer
publisher	Georg Thieme Verlag KG
series	Pharmaceutical Fronts
issn	2628-5088 2628-5096
publishDate	2021-03-01
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.
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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Discovery of SIPI6473, a New, Potent, and Orally Bioavailable Multikinase Inhibitor for the Treatment of Non-small Cell Lung Cancer

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