New Histone Demethylase LSD1 Inhibitor Selectively Targets Teratocarcinoma and Embryonic Carcinoma Cells
Bioorganic and Medicinal Chemistry
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LSD1/KDM1 is a histone demethylase that preferentially removes methyl groups from the mono- and di-methylated lysine 4 in histone H3 (H3K4), key marks for active chromatin for transcriptional activation. LSD1 is essential for pluripotent embryonic stem cells and embryonic teratocarcinoma/carcinoma cells and its expression is often elevated in various cancers. We developed a new LSD1 inhibitor, CBB3001, which potently inhibited LSD1 activity both in vitro and in vivo. CBB3001 also selectively inhibited the growth of human ovarian teratocarcinoma PA-1 and mouse embryonic carcinoma F9 cells, caused the downregulation of pluripotent stem cell proteins SOX2 and OCT4. However, CBB3001 does not have significant inhibition on the growth of human colorectal carcinoma HCT116 cells or mouse fibroblast NIH3T3 cells that do not express these stem cell proteins. Our studies strongly indicate that CBB3001 is a specific LSD1 inhibitor that selectively inhibits teratocarcinoma and embryonic carcinoma cells that express SOX2 and OCT4.
CBB3001; Embryonic carcinoma; Histone demethylase; LSD1/KDM1 inhibitor; Methylated H3K4 of Histone H3; OCT4; SOX2; Teratocarcinoma
Medicinal Chemistry and Pharmaceutics
New Histone Demethylase LSD1 Inhibitor Selectively Targets Teratocarcinoma and Embryonic Carcinoma Cells.
Bioorganic and Medicinal Chemistry, 26(8),