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Target deconvolution of bioactive small molecules: the heart of chemical biology and drug discovery

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Abstract

Identification of the target proteins of bioactive small molecules isolated from phenotypic screens plays an important role in chemical biology and drug discovery. However, discovering the targets of small molecules is often the most challenging and time-consuming step for chemical biology researchers. To overcome the bottlenecks in target identification, many new approaches based on genomics, proteomics, and bioinformatics technologies have been developed. Here, we provide an overview of the current major methodologies for target deconvolution of bioactive small molecules. To obtain an integrated view of the mechanisms of action of small molecules, we propose a systematic approach that involves the combination of multi-omics-based target identification and validation and preclinical target validation.

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Acknowledgments

This study was partly supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean Government (2010-0017984 and 2012M3A9D1054520), the Translational Research Center for Protein Function Control, KRF (2009-0083522), the Ministry of Health & Welfare (0620360-1), the Basic Science Research Program, the Ministry of Education (NRF-2014R1A1A2057902), and the Brain Korea 21 Plus Project, Republic of Korea.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Republic of Korea

    Hye Jin Jung

  2. Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea

    Ho Jeong Kwon

  3. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, 120-752, Republic of Korea

    Ho Jeong Kwon

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  1. Hye Jin Jung
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Jung, H.J., Kwon, H.J. Target deconvolution of bioactive small molecules: the heart of chemical biology and drug discovery. Arch. Pharm. Res. 38, 1627–1641 (2015). https://doi.org/10.1007/s12272-015-0618-3

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  • DOI: https://doi.org/10.1007/s12272-015-0618-3

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