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基于伊索克萨的VEGFR2抑制的合理药物发现

Shital M Patil¹, Indrani Mahadik¹, Shashikant V Bhandari¹

¹Department of Chemistry, AISSMS College of Pharmacy, Kennedy Road, Pune, 01, India.

Current drug discovery technologies

|May 27, 2024

概括

定量结构-活性关系 (QSAR) 研究确定了强大的血管内皮生长因子受体2 (VEGFR2) 抑制剂的关键结构特征. 这些优化的化合物通过阻断瘤血管生成和转移,显示出有前途的抗癌潜力.

科学领域:

药用化学医学化学
计算化学计算化学
癌症治疗方法癌症治疗方法

背景情况:

受体氨酸激酶 (RTK) 信号通路是癌症治疗中的关键目标.
血管内皮生长因子受体2 (VEGFR2) 对于瘤血管生成和转移至关重要.
抑制VEGFR2可以阻碍瘤生长和扩散.

研究的目的:

使用定量结构-活性关系 (QSAR) 分析,开发一种针对VEGFR2抑制的优化药.
阐明化学结构与新化学实体 (NCE) 的VEGFR2抑制活性之间的关系.

主要方法:

使用多线性回归 (MLR) 方法进行了定量结构-活动关系 (QSAR) 建模.
使用QSARINS v.2.2.4软件进行模型生成.
进行了分子对接研究,以评估结合 afinities.

主要成果:

2D QSAR模型实现了高的相关系数 (R2=0.9396).
三维QSAR模型显示出强大的预测能力 (R2=0.9121,Q2=0.8377).
大多数衍生品表现出显著的VEGFR2抑制潜力,得到了对接和毒性分析的支持.

结论:

附在异醇部分的环上的电子捐赠组增强了VEGFR2抑制活性.
这些化合物在VEGFR2.2中对关键氨基酸 (Cys:919,Asp:1046,Glu:885) 具有很高的亲和力.
所有研究的新化学实体 (NCE) 都遵循利宾斯基的五项规则,表明它们具有有利的药理动力学特性.

关键词:

在MLR中,MLR是MLR.在QSAR中使用QSAR.卡萨林斯 (QSARINS) 是一个名字.在VEGFR2的基础上,VEGFR2 伊索克萨醇衍生物的使用.施罗丁格. 施罗丁格.

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