Yi-Chao Zheng, Jiao Chang, Ting Zhang , Feng-Zhi Suo , Xiao-Bing Chen, Ying Liu , Bing Zhao, Bin Yu* and Hong-Min Liu* Pages 2496 - 2504 ( 9 )
Background: In the past few years, great of attention has been paid to the identification and characterization of selective and potent inhibitors of the first identified histone demethylase LSD1, which may erase mono- and di-methylated histone 3 lysine 4 and 9. As the aberrant overexpression of LSD1 is involved in various pathological processes, especially cancer, obtaining selective and potent LSD1 inhibitors has emerged as a crucial issue in medicinal chemistry research.
Method: Until now, several LSD1 inhibitor screening models have been established, including enzyme coupled assay, LC-MS based assay, and FRET based assay. Nevertheless, due to some special instrument requirement and additional costs of LC-MS and FRET, the enzyme coupled assay is the most widely applied method for LSD1 inhibitor screening. Result: We summarized and compared several reported in vitro LSD1 inhibitor screening models. Each of them has distinct advantages and disadvantages, and none of these methods is perfect. In order to exclude the false positive results, at least one additional method should be applied to screen LSD1 inhibitors.LSD1, inhibitor, screening model, enzyme coupled assay, LC-MS, FRET.
Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China; Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety; Institute of Drug Discovery and Development; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China; Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety; Institute of Drug Discovery and Development; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China; Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety; Institute of Drug Discovery and Development; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China; Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety; Institute of Drug Discovery and Development; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, Henan 450001, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China; Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety; Institute of Drug Discovery and Development; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China; Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety; Institute of Drug Discovery and Development; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, School of Pharmaceutical Sciences, Zhengzhou University, P.O. Box: 450001, Zhengzhou, School of Pharmaceutical Sciences, Zhengzhou University, P.O. Box: 450001, Zhengzhou