Chair and Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, ul. Grunwaldzka 6, 60-780 Poznań, Poland.
Faculty of Chemical Engineering and Technology, Cracow University of Technology, ul. Warszawska 24, 31-155 Kraków, Poland.
Int J Mol Sci. 2020 Jul 7;21(13):4793. doi: 10.3390/ijms21134793.
Vascular endothelial growth factor receptor 2 (VEGFR2) is a key receptor in the angiogenesis process. The VEGFR2 expression is upregulated in many cancers so this receptor is an important target for anticancer agents. In the present paper, we analyse interactions of several dimeric indazoles, previously investigated for anticancer activity, with the amino acids present in the VEGFR2 binding pocket. Using the docking method and MD simulations as well as theoretical computations (SAPT0, PIEDA, semi-empirical PM7), we confirmed that these azoles can efficiently bind into the kinase pocket and their poses can be stabilised by the formation of hydrogen bonds, π-π stacking, π-cation, and hybrid interactions with some amino acids of the kinase cavity like Ala866, Lys868, Glu885, Thr916, Glu917, and Phe918.
血管内皮生长因子受体 2（VEGFR2）是血管生成过程中的关键受体。VEGFR2 的表达在许多癌症中上调，因此该受体是抗癌药物的重要靶点。在本文中，我们分析了几种先前研究过的二聚吲哚与 VEGFR2 结合口袋中存在的氨基酸的相互作用。使用对接方法和 MD 模拟以及理论计算（SAPT0、PIEDA、半经验 PM7），我们证实这些唑类化合物可以有效地结合到激酶口袋中，并且它们的构象可以通过形成氢键、π-π 堆积、π-阳离子和与激酶腔中的一些氨基酸（如 Ala866、Lys868、Glu885、Thr916、Glu917 和 Phe918）的混合相互作用来稳定。
