Title

New Histone Demethylase LSD1 Inhibitor Selectively Targets Teratocarcinoma and Embryonic Carcinoma Cells

Document Type

Article

Publication Date

2-7-2018

Publication Title

Bioorganic and Medicinal Chemistry

Volume

26

Issue

8

First page number:

1523

Last page number:

1537

Abstract

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.

Keywords

CBB3001; Embryonic carcinoma; Histone demethylase; LSD1/KDM1 inhibitor; Methylated H3K4 of Histone H3; OCT4; SOX2; Teratocarcinoma

Disciplines

Medicinal Chemistry and Pharmaceutics

Language

English

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