Niles Andrew L, Moravec Richard A, Riss Terry L
Research Department, Promega Corporation, 2800 Woods Hollow Road, Madison, WI, USA.
Curr Chem Genomics. 2009 Jun 11;3:33-41. doi: 10.2174/1875397300903010033.
In vitro cytotoxicity testing has become an integral aspect of drug discovery because it is a convenient, costeffective, and predictive means of characterizing the toxic potential of new chemical entities. The early and routine implementation of this testing is testament to its prognostic importance for humans. Although a plethora of assay chemistries and methods exist for 96-well formats, few are practical and sufficiently sensitive enough for application in high throughput screening (HTS). Here we briefly describe a handful of the currently most robust and validated HTS assays for accurate and efficient assessment of cytotoxic risk. We also provide guidance for successful HTS implementation and discuss unique merits and detractions inherent in each method. Lastly, we discuss the advantages of combining specific HTS compatible assays into multi-parametric, same-well formats.
体外细胞毒性测试已成为药物研发中不可或缺的一部分,因为它是一种便捷、经济高效且能预测新化学实体潜在毒性的手段。这种测试的早期和常规实施证明了其对人类的预后重要性。尽管存在大量适用于96孔板形式的检测化学方法和手段,但很少有方法既实用又足够灵敏以应用于高通量筛选(HTS)。在此,我们简要描述一些目前最为可靠且经过验证的用于准确高效评估细胞毒性风险的HTS检测方法。我们还提供了成功实施HTS的指导,并讨论了每种方法固有的独特优点和缺点。最后,我们讨论了将特定的HTS兼容检测方法组合成多参数、同孔形式的优点。