1. Academic Validation
  2. Dual inhibitors of LSD1 and spermine oxidase

Dual inhibitors of LSD1 and spermine oxidase

  • Medchemcomm. 2019 Feb 8;10(5):778-790. doi: 10.1039/c8md00610e.
Steven Holshouser 1 Matthew Dunworth 2 Tracy Murray-Stewart 2 Yuri K Peterson 1 Pieter Burger 1 Joy Kirkpatrick 1 Huan-Huan Chen 1 Robert A Casero Jr 2 Patrick M Woster 1
Affiliations

Affiliations

  • 1 Department of Drug Discovery and Biomedical Sciences , Medical University of South Carolina , 70 President St. , Charleston , SC 29425 , USA . Email: woster@musc.edu.
  • 2 Sidney Kimmel Comprehensive Cancer Center , Johns Hopkins School of Medicine , 1650 Orleans St. Room 551 , Baltimore , MD 21287 , USA.
Abstract

We have previously described the synthesis and evaluation of 3,5-diamino-1,2,4-triazole analogues as inhibitors of the flavin-dependent Histone Demethylase LSD1. These compounds are potent inhibitors of LSD1 without activity against monoamine oxidases A and B, and promote the elevation of H3K4me2 levels in tumor cells in vitro. We now report that the cytotoxicity of these analogues in pancreatic tumor cells correlates with the overexpression of LSD1 in each tumor type. In addition, we show that a subset of these 3,5-diamino-1,2,4-triazole analogues inhibit a related flavin-dependent oxidase, the polyamine catabolic Enzyme spermine oxidase (SMOX) in vitro.

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