Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
Bioorg Med Chem. 2012 Mar 15;20(6):1922-8. doi: 10.1016/j.bmc.2011.11.021. Epub 2011 Nov 20.
For effective bioactive small molecule discovery and development into new therapeutic drug, a systematic screening and target protein identification is required. Different from the conventional screening system, herein phenotypic screening in combination with multi-omics-based target identification and validation (MOTIV) is introduced. First, phenotypic screening provides visual effect of bioactive small molecules in the cell or organism level. It is important to know the effect on the cell or organism level since small molecules affect not only a single target but the entire cellular mechanism within a cell or organism. Secondly, MOTIV provides systemic approach to discover the target protein of bioactive small molecule. With the chemical genomics and proteomics approach of target identification methods, various target protein candidates are identified. Then network analysis and validations of these candidates result in identifying the biologically relevant target protein and cellular mechanism. Overall, the combination of phenotypic screening and MOTIV will provide an effective approach to discover new bioactive small molecules and their target protein and mechanism identification.
为了有效地发现具有生物活性的小分子并将其开发成新的治疗药物，需要进行系统的筛选和靶蛋白鉴定。与传统的筛选系统不同，本文介绍了表型筛选与基于多组学的靶标鉴定和验证（MOTIV）相结合的方法。首先，表型筛选提供了生物活性小分子在细胞或生物体水平上的可视化效果。了解对细胞或生物体水平的影响很重要，因为小分子不仅会影响单个靶标，还会影响细胞或生物体内部的整个细胞机制。其次，MOTIV 提供了系统性的方法来发现生物活性小分子的靶蛋白。通过化学基因组学和蛋白质组学的靶标鉴定方法，可以鉴定出各种靶蛋白候选物。然后，对这些候选物进行网络分析和验证，可确定具有生物学相关性的靶蛋白和细胞机制。总的来说，表型筛选和 MOTIV 的结合将为发现新的生物活性小分子及其靶蛋白和机制鉴定提供一种有效的方法。
