The lysine methyltransferase G9a is overexpressed in many human cancers. UNC0646 is a potent G9a inhibitor with an IC50 value of 6nM in the SAHH-coupled assay. The H3K9me2 antibody cell immunofluorescence In-Cell Western (ICW) assay showed that the IC50 values of UNC0646 for reducing H3K9me2 levels in MDA-MB-231, MCF7, PC3, 22RV1, HCT116 wt, HCT116 p53−/−, and IMR90 cell lines were 26, 10, 12, 14, 68, 86, and 10nM, respectively. The toxicity (EC50) of UNC0646 in these cell lines were 3.3, 4.7, 2.8, 7.2, 8.7, 12, and 3.6μM, respectively. UNC0646 is also a potent GLP inhibitor with an IC50 value of < 15nM[2]. In an orthotopic hepatocellular carcinoma mouse model, nanodiamond-mediated delivery of UNC0646 at a dosage of 2mg/kg significantly inhibited tumor growth compared to the control groups. The ND-UNC0646 treated group also showed minimal positive Ki67 staining, no tissue morphological alterations or inflammation in tumor tissues[3].
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