Luesch Hendrik
Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA.
Mol Biosyst. 2006 Dec;2(12):609-20. doi: 10.1039/b609384a. Epub 2006 Oct 27.
Drug discovery is hampered by the lack of general strategies to characterize the mechanisms of action and intracellular targets of bioactive small molecules. Genomics and proteomics promise to aid in this process. Genome-wide approaches in yeast have proven useful to infer the targets and target pathways of small molecules. These approaches are being systematically transferred into mammalian cell culture systems in order to interrogate more complex pathways in a more relevant setting. Advances in proteomics and in vivo genetic screening in multicellular model organism systems are also becoming increasingly powerful and amenable to high-throughput. Current methodologies and technologies are discussed, including how these global approaches complement affinity-based target identification strategies.
缺乏用于表征生物活性小分子作用机制和细胞内靶点的通用策略阻碍了药物发现。基因组学和蛋白质组学有望助力这一过程。酵母中的全基因组方法已被证明有助于推断小分子的靶点和靶点途径。这些方法正在被系统地应用于哺乳动物细胞培养系统，以便在更相关的环境中研究更复杂的途径。蛋白质组学以及多细胞模式生物系统中的体内遗传筛选方面的进展也日益强大且适用于高通量研究。本文讨论了当前的方法和技术，包括这些全局性方法如何补充基于亲和力的靶点识别策略。
