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Discovery of Dioxino2,3-fquinazoline derivative VEGFR-2 inhibitors exerting significant antipro-liferative activity in HUVECs and mice.

08:00 EDT 17th April 2019 | BioPortfolio

Summary of "Discovery of Dioxino2,3-fquinazoline derivative VEGFR-2 inhibitors exerting significant antipro-liferative activity in HUVECs and mice."

Twelve 2,3-dihydro-[1,4]-dioxino[2,3-f]quinazoline derivatives were designed and evaluated as vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors. The most half-maximal inhibitory concentration (IC) values of them were less than 10 nM. Among these compounds, 13d displayed highly effective inhibitory activity against VEGFR-2 (IC = 2.4 nM) and excellent antiproliferative activities against human umbilical vein endothelial cells (HUVECs) (IC = 1.2 nM). When anti-tumor animal experiments were carried out in mice, the tumor almost disappeared (TGI = 133.0%) after six days of administration of 13d. Therefore, 13d was a potential and effective anticancer agent. The binding conformations were respectively compared between VEGFR-2 with 13d and leading compound lenvatinib, and shows that they have similar binding modes.

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This article was published in the following journal.

Name: European journal of medicinal chemistry
ISSN: 1768-3254
Pages: 349-356

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