title: Discovery of novel drug targets and their functions using phenotypic screening of natural products.
abstract: Natural products are valuable resources that provide a variety of bioactive compounds and natural pharmacophores in modern drug discovery. Discovery of biologically active natural products and unraveling their target proteins to understand their mode of action have always been critical hurdles for their development into clinical drugs. For effective discovery and development of bioactive natural products into novel therapeutic drugs, comprehensive screening and identification of target proteins are indispensable. In this review, a systematic approach to understanding the mode of action of natural products isolated using phenotypic screening involving chemical proteomics-based target identification is introduced. This review highlights three natural products recently discovered via phenotypic screening, namely glucopiericidin A, ecumicin, and terpestacin, as representative case studies to revisit the pivotal role of natural products as powerful tools in discovering the novel functions and druggability of targets in biological systems and pathological diseases of interest.
authors.affiliation: Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea.
authors.forename: Junghwa
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea. kwonhj@yonsei.ac.kr.|Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, 120-752, Republic of Korea. kwonhj@yonsei.ac.kr.
authors.forename: Ho Jeong
authors.identifier: http://orcid.org/0000-0002-6919-833X
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D001688:Biological Products / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D058990:Molecular Targeted Therapy; D010456:Peptides, Cyclic / Q000494:pharmacology; D040901:Proteomics; D047630:Depsipeptides
chemical_list: D000617:Aminoglycosides; D001688:Biological Products; D001643:Bridged Bicyclo Compounds; D010456:Peptides, Cyclic; C000596518:ecumicin; D047630:Depsipeptides; C052314:glucopiericidin A; C080890:terpestacin
keywords: Drug discovery; Mode of action; Natural products; Phenotypic screening; Target identification