Uses
CBB1007 is a cell-permeable amidino-guanidinium compound that acts as a potent, reversible and substrate competitive LSD1 selective inhibitor (IC50 = 5.27 μM for hLSD1).
IC50 Value: 5.27 uM
Target: hLSD1
CBB1007 efficiently can block LSD1-mediated demethylation of H3K4Me2 and H3K4Me (IC50 ≤ 5 μM) with no effect on H3K4Me3 and H3K9Me2, and LSD2 and JARID1A activities. Increases H3K4Me2 and H3K4Me contents (IC50 ≤ 5 μM), and causes activation of epigenetically suppressed CHRM4/M4-ArchR and SCN3A genes in F9 cells (IC50 ≤ 3.74 μM). CBB1007 was Shown to preferentially arrest the growth of pluripotent tumors with minimal effect on non-pluripotent cancer or normal somatic cells (IC50 ≥ 100 μM).
Biological Activity
cbb1007 is an inhibitor of histone demethylase lsd1with ic50 values of 5.27μm [1].lsd1 is a member of the fad-dependent amine oxidase family. it converts di-methylated h3k4 to mono- and un-methylated h3k4 and suppresses gene expression. as an inhibitor of lsd1, cbb1007 is developed to understand the function of the enzyme. in the in vitro assay, cbb1007 shows highly potent inhibitory activity with ic50 value of 5.27μm. it is specific against lsd1 and has no effect on other histone demethylases including lsd2 and jarid1a. in the mouse f9 embryonic teratocarcinoma cells, cbb1007 cause a reproducible increase of mono- and di-methylated h3k4 with ic50 value of 1μm-5μm. it also activates the expression of chrm4 and scn3a which are the target genes of lsd1. the inhibition of lsd1 results in the growth inhibition of these cells. furthermore, cbb1007 is found to inhibit the proliferation of other pluripotent cancer cells as well as the embryonic stem cells that express the stem cell markers oct4 and sox2 [1].
References
[1] wang j, lu f, ren q, et al. novel histone demethylase lsd1 inhibitors selectively target cancer cells with pluripotent stem cell properties. cancer research, 2011, 71(23): 7238-7249.
