<p style=/line-height:25px/>UNC0638 is an inhibitor of protein lysine methyltransferases G9a(IC50<15 nM) and GLP(IC50=19 nM) with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets.<br>IC50 value: <15 nM (G9a); 19±1 nM (GLP) [1]<br>Target: Protein lysine methyltransferases G9a/GLP<br>in vitro: UNC0638 was a potent G9a (IC50 < 15 nM (n = 4)) and GLP inhibitor (IC50 = 19 ± 1 nM (n = 2)) in these SAHH-coupled assays. UNC0638 also stabilized G9a and GLP in differential scanning fluorimetry (DSF) experiments, with Tm shifts of 4 °C and 8 °C, respectively, consistent with high-affinity binding [1]. Of note, UNC0638 had weak but measurable activity against JMJD2E (IC50 = 4,500 ± 1,100 nM (n = 3)), a Jumonji protein demethylase and DNA methyltransferase DNMT1 (IC50 = 107,000 ± 6,000 nM (n = 2)). Nevertheless, the selectivity of UNC0638 for G9a and GLP over JMJD2E was >200-fold, and selectivity for G9a and GLP over DNMT1 was >5,000-fold [1]. In MDA-MB-231 cells, UNC0638 (48 h exposure) reduced H3K9me2 levels in a concentration-dependent manner with an IC50 of 81 ± 9 nM (n = 3), which indicates considerably higher potency than BIX01294 (IC50 = 500 ± 43 nM (n = 3)) [1]. UNC0638 could efficiently reduce H3K9me2 levels of cultured sheep foetal fibroblast cells in a concentration-dependent manner. Cloned embryos were subsequently produced from UNC0638-treated donor cells with down-regulated H3K9me2, but their in vitro development was not improved when compared with the control [2].<br>in vivo:<br></p>
