早期人工智能驱动的对现有药物的重新定位研究,将其转化为血管压素V2受体
Daniela Trisciuzzi1, Ines Angelini2, Nicola Gambacorta1
1Department of Pharmacy - Pharmaceutical Sciences, University of Bari Aldo Moro, Italy.
Computers in biology and medicine
|December 26, 2025
概括
这项研究将zafirlukast重新定位为V2受体 (V2R) 抗剂,对水平衡至关重要. 扎菲尔卢卡斯特在细胞模型中有效抑制了V2R活性,显示出治疗相关疾病的潜力.
科学领域:
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- V2受体 (V2R) 是一种G蛋白结合受体 (GPCR),调节脏水平衡.
- 维2R功能障碍与癌症和囊扩大有关.
- 现有的药物为V2R对抗提供了潜在的途径.
研究的目的:
- 为了确定现有的药物,可以重新作为V2R抗剂.
- 在与V2R相关的疾病中探索V2R对抗的潜在治疗应用.
主要方法:
- 利用基于人工智能的平台PLATO,对1882种药物进行反向查,以对抗V2R.
- 雇佣FRET研究和诱导适应对接模拟用于药物验证.
- 在表达人类V2R和AQP2的MCD4细胞上测试了优先级药物.
主要成果:
- 列出了五种潜在的V2R抗剂:卡贝戈林,克洛皮多格雷尔,克洛克萨西林,珀菲纳和扎菲尔卢卡斯特.
- 扎菲尔卢卡斯特在纳米分子度下显著抑制了DDAVP诱导的cAMP产生和水的再吸收.
- 分子对接揭示了zafirlukast与其已知的CysLTR1结合部位相似的V2R部位结合.
结论:
- 扎菲尔卢卡斯特 (Zafirlukast) 作为一种V2R抗剂,与选择性抗剂托尔瓦普坦 (tolvaptan) 相提并论.
- 这些发现支持将扎菲尔卢卡斯特重新用于与V2R相关的治疗策略.
- 这项研究强调了人工智能驱动的药物重定向对GPCR标的潜力.
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