Minor Lisa K
Johnson & Johnson Pharmaceutical Research and Development, LLC, Springhouse Pennsylvania, Welsh & McKean Rds, Springhouse, PA 19477, USA.
Expert Rev Mol Diagn. 2005 Jul;5(4):561-71. doi: 10.1586/14737159.5.4.561.
The development of novel antagonists or agonists of membrane tyrosine kinase receptors is a large focus of discovery research. This review will provide some background on membrane tyrosine kinases as well as a description of some of the better established assays used for the high-throughput screening of membrane tyrosine kinase inhibitors. Biochemical methods detailed include those using labels such as radioactivity and fluorescence (fluorescence energy transfer, fluorescence and fluorescence polarization) as well as label-free assays using luminescence. These assays are solid phase, liquid phase, as well as bead based. In addition, a discussion on which tools are available to screen for membrane tyrosine kinase receptor modulators/activators using whole-cell assays will be presented. The potential clinical need for testing receptor activation/phosphorylation as well as the possibility of using some of these tests to measure biomarkers of disease or as clinical diagnostic tools to tailor drug therapy or monitor its efficacy will also be discussed.
膜酪氨酸激酶受体新型拮抗剂或激动剂的开发是发现研究的一大重点。本综述将提供一些关于膜酪氨酸激酶的背景知识，并描述一些用于高通量筛选膜酪氨酸激酶抑制剂的较为成熟的检测方法。详细介绍的生化方法包括使用放射性和荧光等标记物的方法（荧光能量转移、荧光和荧光偏振）以及使用发光的无标记检测方法。这些检测方法有固相、液相以及基于微珠的方法。此外，还将讨论使用全细胞检测筛选膜酪氨酸激酶受体调节剂/激活剂可利用的工具。还将讨论检测受体激活/磷酸化的潜在临床需求，以及使用其中一些检测方法来测量疾病生物标志物或作为临床诊断工具以定制药物治疗或监测其疗效的可能性。
