高通量SFC-MS/MS方法来测量EPSA和预测人类的透性.
Yue-Ting Wang1, Edward Price1, Mei Feng1
1Quantitative, Translational, and ADME Sciences (QTAS), AbbVie Inc., North Chicago, Illinois 60064, United States.
Journal of medicinal chemistry
|July 8, 2024
概括
一种新的高通量方法 (HT-EPSA) 测量了实验性的极地表面积,以有效地评估早期发现中的药物透性. 该技术改进了预测口服药物吸收和指导化合物选择的现有方法.
科学领域:
- 药物发现和开发 药物发现和开发
- 药理动力学和药物新陈代谢
- 计算化学计算化学
背景情况:
- 药物透性对于口服吸收至关重要,但其早期评估是困难的,特别是对于违反利宾斯基五项规则的人来说.
- 现有的透性评估方法可能耗时,缺乏足够的灵敏度或选择性.
- 准确预测药物透性对于高效的优化和减少后期失效至关重要.
研究的目的:
- 建立一种高通量测量实验极地表面积 (HT-EPSA) 的高通量方法,作为药物透性的体外替代品.
- 评估HT-EPSA在预测人类体外和体外被动透性的有用性.
- 证明HT-EPSA用于排序透性和改善早期药物发现决策的应用.
主要方法:
- 开发一种高通量测定方法来测量实验性极地表面积 (HT-EPSA).
- 将HT-EPSA与数据采集时间,灵敏度,选择性和数据质量方面的传统方法进行比较.
- 应用HT-EPSA来预测Caco-2细胞和人类肠道的透性,包括一个蛋白质溶解向化母的案例研究.
主要成果:
- 与以前的方法相比,HT-EPSA显著减少了数据采集时间,同时提高了敏感性,选择性和数据质量.
- 通过HT-EPSA的测试,可以更好地预测Caco-2细胞和人类肠道的透性,比拓极地表面积和PAMPA.
- 该方法成功地在化向化母的案例研究中对透性进行了排序排序,有助于化合物选择.
结论:
- HT-EPSA方法为评估药物透性提供了强大的和高效的体外替代品.
- 在药物发现过程中,HT-EPSA对早期化合物排序和更快的决策有价值.
- 这种方法对预测体外和体外人体肠道透性充满希望,优化药物开发管道.
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