TCPs: privileged scaffolds for identifying potent LSD1 inhibitors for cancer therapy. (May 2016)

• Record Type: Journal Article
• Authors: Zheng, Yi-Chao; Yu, Bin; Chen, Zhe-Sheng; Liu, Ying; Liu, Hong-Min
• Is Part Of: Epigenomics. Volume 8:Number 5(2016)
• Page Start: 651
• Page End: 666
• Publication Date: 2016-05
• Subjects: cancer -- inhibitor -- LSD1 -- trans-2-phenylcyclopropylamine; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi-2015-0002
• Languages: English
• ISSNs: 1750-1911

Abstract

Since the first lysine-specific demethylase (KDM), lysine-specific demethylase 1 (LSD1), was characterized in 2004, several families of KDMs have been identified. LSD1 can specifically demethylate H3K4me1/2, H3K9me1/2 as well as some nonhistone substrates. It has been demonstrated to be an oncogene as well as a drug target. Hence, tens of small-molecule LSD1 inhibitors have been designed, synthesized and applied for cancer treatment. However, the two LSD1 inhibitors that have been advanced into early phase clinical trials are trans-2-phenylcyclopropylamine (TCP) derivatives, which indicate that TCP is a druggable scaffold for LSD1 inhibitor. Here, we review the design, synthesis and properties of reported TCP-based LSD1 inhibitors as well as their biological roles.