Moellering Raymond E, Cravatt Benjamin F
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Chem Biol. 2012 Jan 27;19(1):11-22. doi: 10.1016/j.chembiol.2012.01.001.
Creating first-in-class medications to treat human disease is an extremely challenging endeavor. While genome sequencing and genetics are making direct connections between mutations and human disorders at an unprecedented rate, matching molecular targets with a suitable therapeutic indication must ultimately be achieved by pharmacology. Here, we discuss how the integration of chemical proteomic platforms (such as activity-based protein profiling) into the earliest stages of the drug discovery process has the potential to greatly expand the scope of proteins that can be pharmacologically evaluated in living systems, and, through doing so, promote the identification and prioritization of new therapeutic targets.
研发治疗人类疾病的首创药物是一项极具挑战性的工作。尽管基因组测序和遗传学正以前所未有的速度将突变与人类疾病直接联系起来，但将分子靶点与合适的治疗适应症相匹配最终必须通过药理学来实现。在此，我们讨论将化学蛋白质组学平台（如基于活性的蛋白质谱分析）整合到药物发现过程的早期阶段如何有可能极大地扩展可在活体系统中进行药理学评估的蛋白质范围，并通过这样做促进新治疗靶点的识别和优先级排序。
