文献类型：期刊文献

英文题名：Design of VEGFR2 Inhibitors: Construction and Screening of Virtual Compound Libraries

作者：Luo, Yixin[1,2,3];Hu, Chunqi[4]

机构：[1]Jinan Univ, Coll Pharm, Int Cooperat Lab Tradit Chinese Med Modernizat, Guangzhou, Peoples R China;[2]Jinan Univ, Coll Pharm, Innovat Drug Discovery Chinese Minist Educ MOE, Guangzhou, Peoples R China;[3]Shaoxing Univ, Dept Med & Hlth, Yuanpei Coll, Shaoxing, Peoples R China;[4]Shaoxing Univ, Dept Pharm, Inst Chem & Chem Engn, Shaoxing 312000, Peoples R China

年份：2024

卷号：21

期号：19

起止页码：4709

外文期刊名：LETTERS IN DRUG DESIGN & DISCOVERY

收录：SCI-EXPANDED(收录号：WOS:001482258200008)、、WOS

基金：This study was nancially supported by National Natural Science Foundation of China (81673294 and 81502926) and Zhejiang Province Public Welfare Projects (2016C33067) and China Postdoctoral Science Foundation (2017M612017). We also extend our heartfelt thanks to the Shaoxing City Higher Education Teaching Reform Research Project (SXSJG202417) for their generous support of this work

语种：英文

外文关键词：VEGFR-2 inhibitor; virtual compound library; molecular docking; molecular dynamics simulation; computer-aided drug design; receptor tyrosine kinases

外文摘要：Objective The current use of Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) inhibitors is often limited by low selectivity and adverse side effects, highlighting the urgent need for novel, highly selective agents targeting this receptor.Methods Based on existing VEGFR-2 inhibitors, we employed computer-aided drug design (CADD) techniques to develop a virtual compound library using active docking fragments. Molecular docking was performed using the configuration of VEGFR-2 as the receptor protein(PDB:4ASD). Comparative analysis and screening identified the most promising inhibitor, which was subsequently validated through molecular dynamics simulations.Results From the virtual library, 10 potential highly active inhibitors were identified. In particular, Compound 9 demonstrated strong binding affinity with the protein configuration, forming four hydrogen bonds during docking. The calculated CODOCKER energy was 39.7315 kcal/mol, with an RMSD of 0.4634 nm and RMSF of 0.3234 nm. Compared to Sorafenib, Compound 9 exhibited superior docking selectivity and activity.Conclusion Computational analyses suggest that Compound 9 is a promising candidate as a highly selective VEGFR-2 inhibitor. Nonetheless, due to the inherent limitations of in silico docking studies, further chemical synthesis and experimental biological validation are required to confirm its potential.