Schirle Markus, Bantscheff Marcus, Kuster Bernhard
Novartis Institutes for BioMedical Research, Inc., Cambridge, MA 02139, USA.
Chem Biol. 2012 Jan 27;19(1):72-84. doi: 10.1016/j.chembiol.2012.01.002.
Preclinical stages in the drug discovery process require a multitude of biochemical and genetic assays in order to characterize the effects of drug candidates on cellular systems and model organisms. Early attempts to apply unbiased proteomic techniques to the identification of protein targets and off-targets as well as to elucidate the mode of action of candidate drug molecules suffered from a striking discrepancy between scientific expectations and what the technology was able to deliver at the time. Dramatic technological improvements in mass spectrometry-based proteomic and chemoproteomic strategies have radically changed this situation. This review, therefore, highlights proteomic approaches suitable for preclinical drug discovery illustrated by recent success stories.
药物发现过程中的临床前阶段需要大量的生化和基因检测，以便表征候选药物对细胞系统和模式生物的影响。早期尝试应用无偏倚蛋白质组学技术来鉴定蛋白质靶点和脱靶效应，以及阐明候选药物分子的作用模式，但当时科学预期与该技术所能提供的结果之间存在显著差异。基于质谱的蛋白质组学和化学蛋白质组学策略的巨大技术进步已从根本上改变了这种情况。因此，本综述重点介绍了适用于临床前药物发现的蛋白质组学方法，并以近期的成功案例加以说明。
