Ĭopeland RA, Solomon ME, Richon VM (2009) Protein methyltransferases as a target class for drug discovery. įog CK, Jensen KT, Lund AH (2007) Chromatin-modifying proteins in cancer. Rea S, Eisenhaber F, O’Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, Allis CD, Jenuwein T (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases. CT13 provides a novel scaffold for further development of analogous synthetic G9a inhibitors. Molecular docking analysis suggested the binding mode of CT13 which occupies the binding site of histone H3 substrate. CT13 showed selective inhibitory activity against G9a and suppressed the level of H3K9me2 in MCF7 human breast cancer cells. The activity of CT13 was determined by biophysical analyses involving MALDI-TOF mass spectrometry and western blot analysis. In this study, we identified protoberberine alkaloid pseudodehydrocorydaline (CT13) as a novel G9a inhibitor, by structure-based virtual screening of in-house library containing natural product compounds. In recent years, genetic, biological, and physiological evidence has established G9a inhibitors as potential chemotherapeutic agents for cancer treatment. The protein lysine methyltransferase G9a, which controls gene expression by epigenetic regulation of H3K9 methylation, is related to various human diseases, including cancer, drug addiction, and mental retardation.
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