Discovery of Novel SMYD3 Inhibitors for the Treatment of Cancer


The histone proteins H2A, H2B, H3 and H4 play a major role in controlling access to the genome and therefore in determining which genes are expressed within a cell. Histones local to a particular gene can undergo a variety of structural modifications which will either activate or silence transcription. This process is controlled by a range of epigenetic proteins.[1]
One important group of epigenetic proteins are the lysine methyl transferases (PKMTs). SMYD3 is a PKMT that is believed to play a key role in the di- and tri-methylation of H3-Lys4 (H3K4), a modification which has been associated with transcriptional activation. SMYD3 is highly expressed in a number of cancers,[2-4] notably hepatocellular carcinoma, colon, breast, and prostate cancer, whilst being absent or showing low levels of expression in many normal tissues. Knock down of SMYD3 in a number of cancer cell lines has been shown to inhibit cell growth.[2-4] Together this suggests that a SMYD3 inhibitor has the potential to be a new treatment for cancer.

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