Identification of potent inhibitors of potential VEGFR2: a graph neural network-based virtual screening and in vitro study.

IF 5.4 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Shengzhen Hou, Shuning Diao, Yuxiang He, Taiying Li, Wenhui Meng, Jinping Zhang
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引用次数: 0

Abstract

VEGFR2 is a transmembrane tyrosine kinase receptor expressed on vascular endothelial cells and is closely associated with tumour cell growth. A comparison of traditional Chinese medicines and natural products with existing VEGFR2 inhibitors revealed that the former exhibited superior anticancer properties while concomitantly showing a reduced incidence of adverse effects. We proposed a novel strategy for screening potential candidates targeting VEGFR2 in a Chinese medicine monomer database using a combination of AI deep learning and structure-based drug design. The graph neural network served as the final predictive model to evaluate the molecular activities within the database, resulting in the selection of six candidate compounds. Kinase inhibition assays showed that the three compounds exhibited significant inhibition of VEGFR2. Molecular docking and molecular dynamics simulations further demonstrated the stability of their binding to VEGFR2. This study identified three compounds that effectively inhibited VEGFR2, making them promising candidates in cancer treatment.

潜在VEGFR2的有效抑制剂的鉴定:基于图神经网络的虚拟筛选和体外研究。
VEGFR2是一种跨膜酪氨酸激酶受体,在血管内皮细胞上表达,与肿瘤细胞生长密切相关。将中药和天然产物与现有的VEGFR2抑制剂进行比较,发现中药具有更好的抗癌特性,同时不良反应发生率降低。我们提出了一种新的策略,利用人工智能深度学习和基于结构的药物设计相结合,在中药单体数据库中筛选靶向VEGFR2的潜在候选药物。图神经网络作为最终的预测模型,对数据库中的分子活性进行评估,从而筛选出6个候选化合物。激酶抑制实验表明,这三种化合物对VEGFR2具有显著的抑制作用。分子对接和分子动力学模拟进一步证明了它们与VEGFR2结合的稳定性。这项研究确定了三种有效抑制VEGFR2的化合物,使它们成为癌症治疗的有希望的候选者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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