Lysine-specific Demethylase Inhibitor (1C)

Lysine-specific Demethylase Inhibitor (1C) is a lysine-specific demethylase inhibitor.

Lysine-specific demethylase 1 (LSD1) is the first of several protein lysine demethylases identified. Through a FAD-dependent oxidative reaction, LSD1 could specifically remove histone H3K4me2 to H3K4me1 or H3K4me0. When forming a complex with androgen receptor, LSD1 alters its substrates to H3K9me2. The LSD1 complex regulates a coordinated histone modification switch via enzymatic activities and histone modification readers.

In vitro: Lysine-specific Demethylase Inhibitor (1C) was identified as a bisguanidine polyamine analogue exhibiting noncompetitive and specific LSD1 inhibition, with 14.1% in vitro LSD1 activity at 10 μM. Lysine-specific Demethylase Inhibitor (1C) at 0.25 μM to 10 μM could significantly and dose-dependently increase methylation at the histone 3 lysine 4 chromatin mark, H3K4me1 and H3K4me2, without affecting global H3K9me2 levels in HCT116 human colon carcinoma cells. Lysine-specific Demethylase Inhibitor (1C) could also induce expression of several epigenetically silenced genes, such as SFRP1, SFRP4, SFRP5, and GATA5, particularly in the case of SFRP4 and SFRP5 [1].

In vivo: Currently, there is no animal in vivo data reported.

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

Reference:
[1] Sharma SK, Wu Y, Steinbergs N, Crowley ML, Hanson AS, Casero RA, Woster PM.  (Bis)urea and (bis)thiourea inhibitors of lysine-specific demethylase 1 as epigenetic modulators.J Med Chem. 2010 Jul 22;53(14):5197-212.