Discovery of lysine-specific demethylase 1 Inhibitors based on enzymatic mechanism

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Selective inhibitors of lysine-specific demethylase 1 (LSD1) are considered to be candidate anticancer agents. Phenylcyclopropylamine (PCPA) is a best-known LSD1 inhibitor, but its potency and selectivity are inadequate. In this study, on the basis of the concept that LSD1 could be potently and selectively inactivated by delivering PCPA directly to the enzyme's active site, LSD1 inhibitors were designed by conjugating PCPA moiety with a lysine moiety as a carrier targeting LSD1. As a result of their synthesis and biological evaluation, LSD1 inhibitors that showed high activity and selectivity were identified.