Pharmacophore modeling and virtual screening studies for new VEGFR-2 kinase inhibitors

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• 作者：Kyungik Lee ; Ki-Woong Jeong ; Yeonjoo Lee ; Ji Yeon Song ; Maeng Sup Kim ; Gwan Sun Lee ; Yangmee Kim
• 关键词：VEGFR-2 ; Virtual screening ; Docking ; Anticancer activity ; Kinase inhibitor
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：November 2010
• 年：2010
• 卷：45
• 期：11
• 页码：5420-5427
• 全文大小：1077 K

文摘

Virtual screening was performed to determine potent vascular endothelial growth factor receptor (VEGFR)-2 kinase inhibitors. A database of approximately 820,000 commercial compounds was used for screening, and 100 compounds were chosen as candidate VEGFR-2 inhibitors through pharmacophore modeling and docking studies. These 100 compounds were purchased to test their biological activities: 10 compounds were found to inhibit the enzyme, with IC₅₀ values ranging from 10 to 1 μM. Compound 1, which has a triazinoindole ring, inhibited the enzymatic activity of VEGFR-2, with an IC₅₀ value of about 1.6 μM, making it the most potent inhibitor of this enzyme. The triazinoindole derivative may therefore serve as the starting point in the design of new VEGFR-2 kinase inhibitors.