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Dual inhibitors of LSD1 and spermine oxidase.

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.

SUBMITTER: Holshouser S

PROVIDER: S-EPMC6533887 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Dual inhibitors of LSD1 and spermine oxidase.

Holshouser Steven S Dunworth Matthew M Murray-Stewart Tracy T Peterson Yuri K YK Burger Pieter P Kirkpatrick Joy J Chen Huan-Huan HH Casero Robert A RA Woster Patrick M PM

MedChemComm 20190208 5

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 <i>in vitro</i>. 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 sho ...[more]

PMID: 31191868

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