Dual inhibitors of LSD1 and spermine oxidase

Steven Holshouser, Matthew Dunworth, Tracy Murray Stewart, Yuri K. Peterson, Pieter Burger, Joy Kirkpatrick, Huan Huan Chen, Robert A Casero, Patrick M. Woster

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)778-790
Number of pages13
JournalMedChemComm
Volume10
Issue number5
DOIs
Publication statusPublished - Jan 1 2019

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

Cite this

Holshouser, S., Dunworth, M., Murray Stewart, T., Peterson, Y. K., Burger, P., Kirkpatrick, J., ... Woster, P. M. (2019). Dual inhibitors of LSD1 and spermine oxidase. MedChemComm, 10(5), 778-790. https://doi.org/10.1039/c8md00610e