Histone demethylase

Reversible histone lysine methylation is a major mechanism for regulating chromatin dynamics and gene expression. Histone demethylases (EC 1.14.11.) are believed to be involved in tumor-suppressive activities. These are Fe2+- and α-ketoglutarate-dependent oxygenases that are essential components of regulatory transcriptional chromatin complexes. Until recently, the absence of any selective inhibitors hampered the elucidation of the biological relevance of the demethylase activity of JMJ enzymes in regulating cellular responses. The discovery of the selective inhibitors GSK J1 and its ethyl ester prodrug GSK J4 (Axon 1934 and 1933 resp.) has recently shown the importance as critical determinants of pro-inflammatory gene activation in human primary macrophages[1].
The mono- and di-methyl lysine demethylase (LSD1 or KDM1A; EC 1.14.11.xx) is a flavin-bound epigenetic enzyme that oxidatively cleaves methyl groups from monomethyl and dimethyl Lys4 of histone H3 (H3K4Me1, H3K4Me2) and can contribute to gene silencing. Based on its enzymatic mechanism, LSD1 cannot demethylate trimethylated H3K4Me3, but members of the iron-dependent JMJ histone demethylases are known to serve this function. LSD1 is highly expressed in patients with acute myloid leukemia AML, and its overexpression has been implicated in various other tumors. Collectively, these data predicted that the use of small-molecule inhibitors that target LSD1 could result in epigenetic reprogramming that enhanced or facilitated the execution of the ATRA-induced differentiation program in AML cells[2],[3].


[1] A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. L.Kruidenier et al. Nature 2012, 488, 404-408.
[2] P. Prusevich et al. A selective phenelzine analogue inhibitor of histone demethylase LSD1.ACS Chem. Biol. 2014, 9, 1284-1293.
[3] T. Schenk et al. Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nat. Med. 2012, 18, 605-611.

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Axon ID Name Description From price
2306 Bizine Potent LSD1 inhibitor with selectivity over MAO-A/B, and LSD2 €120.00
2622 CPI 4203 Selective inhibitor of KDM5 demethylases (H3K4 specific) €85.00
2573 CPI 455 Selective inhibitor of KDM5 demethylases (H3K4 specific) €95.00
1934 GSK J1 Histone demethylase JMJD3/UTX inhibitor €105.00
1933 GSK J4 Histone demethylase JMJD3/UTX inhibitor €105.00
2375 GSK-LSD1 Irreversible inhibitor of the KDM1 family histone demethylase LSD1 €110.00
2160 JIB 04 Jumonji histone demethylase inhibitor €90.00
2081 ML 324 dihydrochloride Inhibitor of JMJD2 histone demethylase €125.00
2077 OG-L002 hydrochloride Inhibitor of lysine specific demethylase 1 (LSD1 aka KDM1A) €125.00
2674 YUKA1 Selective inhibitor of KDM5A demethylase €125.00

10 Item(s)

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