Ferrick David A, Neilson Andy, Beeson Craig
Seahorse Bioscience, North Billerica, MA, USA.
Drug Discov Today. 2008 Mar;13(5-6):268-74. doi: 10.1016/j.drudis.2007.12.008. Epub 2008 Feb 13.
Cell-based assays have become a favored format for drug discovery because living cells have relevant biological complexity and can be highly multiplexed to screen for drugs and their mechanisms. In response to a changing extracellular environment, disease and/or drug exposure, cells remodel bioenergetic pathways in a matter of minutes to drive phenotypic changes associated with these perturbations. By measuring the extracellular flux (XF), that is the changes in oxygen and proton concentrations in the media surrounding cells, one can simultaneously determine their relative state of aerobic and glycolytic metabolism, respectively. In addition, XF is time-resolved and non-invasive, making it an attractive format for studying drug effects in vitro.
基于细胞的检测方法已成为药物发现中备受青睐的形式,因为活细胞具有相关的生物学复杂性,并且可以高度多重化以筛选药物及其作用机制。响应不断变化的细胞外环境、疾病和/或药物暴露,细胞在几分钟内重塑生物能量途径,以驱动与这些扰动相关的表型变化。通过测量细胞外通量(XF),即细胞周围培养基中氧气和质子浓度的变化,可以分别同时确定它们有氧代谢和糖酵解代谢的相对状态。此外,XF具有时间分辨性且非侵入性,使其成为体外研究药物作用的有吸引力的形式。