Ki(inact) = 59 nM

Bizine is a LSD1 inhibitor.

Lysine-specific demethylase 1 (LSD1), an epigenetic enzyme, can oxidatively cleave methyl groups from monomethyl and dimethyl Lys4 of histone H3 and can also contribute to gene silencing.

In vitro: In a previous study, bizine, a novel phenelzine analogue with a phenyl-butyrylamide appendage, was foundto be a potent in vitro LSD1 inhibitor and was selective against monoamine oxidases A/B and LSD2, the LSD1 homologue. Moreover, in cancer cells, bizine was shown to be effective at modulating bulk histone methylation and the ChIP-seq experiment demonstrated a statistically significant overlap in the H3K4 methylation pattern of genes affected by bizine and those altered in LSD1-/- cells. In addition, the treatment of two cancer cell lines, LNCaP and H460, with bizine led to a reduction in proliferation rate, and bizine also showed additive to synergistic effects on cell growth when used in combination with two tested HDAC inhibitors. Furthermore, neurons exposed to oxidative stress could be protected by the treatment of bizine, indicating its potential applications in neurodegenerative disease [1].

In vivo: Up to now, there is no animal in vivo data reported.

Clinical trial: So far, no clinical study has been conducted.

Reference:
[1] Prusevich, P. ,Kalin, J.H.,Ming, S.A., et al. A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem Biol. 9, 1284-1293 (2014).