VEGFR2, vascular endothelial growth factor receptor 2, plays an important role in anti-angiogenesis and is an effective target for inhibiting tumor cell proliferation and metastasis. Many small molecule inhibitors have so far exhibited fine therapeutic effects but do not rule out some adverse reactions. From the perspective of the new use of old drugs, we use a combination of two different docking methods, molecular dynamics simulations and quantum-chemical calculations to acquire potential anti-angiogenesis inhibitors from the library of FDA-approved drugs. We attain five FDA-approved old drugs from Drugbank as potential inhibitors against VEGFR2. Therein, the anti-tumor effects of three compounds, including vilazodone (psychiatric drug), pranlukast and zafirlukast (asthma drugs), have been reported by previous experiments but no anti-tumor data is available for the other two compounds, including antrafenine (analgesic and anti-inflammatory drug) and iloperidone (psychiatric drug). These five compounds exhibit more stable interaction than sorafenib as a market-oriented drug targeting VEGFR2. In parallel, there is a most stable interaction for zafirlukast while a weakest interaction for iloperidone with VEGFR2. We show that these five compounds bind with the hydrophobic cavity of VEGFR2, then forming hydrogen bond interactions with three key residues, Glu-885, Cys-919 and Asp-1046. Lys-868 and Phe-1047 play an important role in stabilizing the interaction conformation. The binding poses of pranlukast and vilazodone are similar to that of sorafenib, whereas antrafenine and zafirlukast act differently from sorafenib, focusing on the direction difference of the respective ring structure. This work may help to develop new and effective anti-angiogenic inhibitors.

VEGFR2，血管内皮生长因子受体2，在抗血管生成中起重要作用，并且是抑制肿瘤细胞增殖和转移的有效靶标。迄今为止，许多小分子抑制剂均表现出良好的治疗作用，但不排除某些不良反应。从旧药的新用途来看，我们结合使用两种不同的对接方法，分子动力学模拟和量子化学计算，从FDA批准的药物库中获得潜在的抗血管生成抑制剂。我们从Drugbank获得了五种经FDA批准的旧药，作为VEGFR2的潜在抑制剂。其中，三种化合物的抗肿瘤作用包括维拉唑酮（精神药物），普仑司特和扎鲁司特（哮喘药），先前的实验已报道了该药，但尚无其他两种化合物的抗肿瘤数据，包括阿曲芬宁（镇痛和抗炎药）和伊潘立酮（精神病药）。这五种化合物显示出比索拉非尼更稳定的相互作用，而索拉非尼是靶向VEGFR2的市场导向药物。同时，扎鲁司特的相互作用最稳定，而伊立立酮与VEGFR2的相互作用最弱。我们显示这五个化合物与VEGFR2的疏水腔结合，然后与三个关键残基Glu-885，Cys-919和Asp-1046形成氢键相互作用。Lys-868和Phe-1047在稳定相互作用构象中起重要作用。普鲁司特和维拉唑酮的结合姿势与索拉非尼相似，而阿曲芬宁和扎鲁司特的作用与索拉非尼不同，着眼于各个环结构的方向差异。这项工作可能有助于开发新的有效的抗血管生成抑制剂。