Whitebread Steven, Hamon Jacques, Bojanic Dejan, Urban Laszlo
PreClinical Profiling, Lead Discovery Center, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Drug Discov Today. 2005 Nov 1;10(21):1421-33. doi: 10.1016/S1359-6446(05)03632-9.
Broad-scale in vitro pharmacology profiling of new chemical entities during early phases of drug discovery has recently become an essential tool to predict clinical adverse effects. Modern, relatively inexpensive assay technologies and rapidly expanding knowledge about G-protein coupled receptors, nuclear receptors, ion channels and enzymes have made it possible to implement a large number of assays addressing possible clinical liabilities. Together with other in vitro assays focusing on toxicology and bioavailability, they provide a powerful tool to aid drug development. In this article, we review the development of this tool for drug discovery, its appropriate use and predictive value.
在药物发现的早期阶段，对新化学实体进行大规模体外药理学分析已成为预测临床不良反应的重要工具。现代相对廉价的检测技术以及对G蛋白偶联受体、核受体、离子通道和酶的认识迅速扩展，使得开展大量针对潜在临床风险的检测成为可能。与其他专注于毒理学和生物利用度的体外检测方法一起，它们为辅助药物开发提供了强大工具。在本文中，我们回顾了这一药物发现工具的发展、其合理应用及预测价值。
