Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Pediatric Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02215, USA.
Br J Cancer. 2012 Jan 17;106(2):254-61. doi: 10.1038/bjc.2011.543. Epub 2011 Dec 13.
While target-based small-molecule discovery has taken centre-stage in the pharmaceutical industry, there are many cancer-promoting proteins not easily addressed with a traditional target-based screening approach. In order to address this problem, as well as to identify modulators of biological states in the absence of knowing the protein target of the state switch, alternative phenotypic screening approaches, such as gene expression-based and high-content imaging, have been developed. With this renewed interest in phenotypic screening, however, comes the challenge of identifying the binding protein target(s) of small-molecule hits. Emerging technologies have the potential to improve the process of target identification. In this review, we discuss the application of genomic (gene expression-based), genetic (short hairpin RNA and open reading frame screening), and proteomic approaches to protein target identification.
虽然基于靶点的小分子发现已经成为制药行业的焦点，但仍有许多促进癌症发生的蛋白质，这些蛋白质不容易通过传统的基于靶点的筛选方法来解决。为了解决这个问题，以及在不知道状态转换的蛋白质靶点的情况下识别生物状态的调节剂，已经开发了替代表型筛选方法，如基于基因表达和高内涵成像的方法。然而，随着对表型筛选的重新关注，也带来了识别小分子命中物的结合蛋白靶点的挑战。新兴技术有可能改善靶点识别的过程。在这篇综述中，我们讨论了基因组（基于基因表达）、遗传（短发夹 RNA 和开放阅读框筛选）和蛋白质组学方法在蛋白质靶点识别中的应用。
