UNC0638 is an inhibitor of G9a and GLP with remarkable potency and selectivity across a wide array of epigenetic and non-epigenetic targets. The Ki value of UNC0638 is determined to be 3.0±0.05 nM (n=2), consistent with the Morrison Ki value of 3.7±0.2 nM (n=3). UNC0638 exhibits notable selectivity over various epigenetic targets, including H3K9 (SUV39H1 and SUV39H2), H3K27 (EZH2), H3K4 (SETD7, MLL, and SMYD3), H3K79 (DOT1L), and H4K20 (SETD8) methyltransferases, as well as PRDM1, PRDM10, and PRDM12. Additionally, UNC0638 displays inactivity against protein arginine methyltransferases PRMT1 and PRMT3, and HTATIP, a histone acetyltransferase. Although UNC0638 exhibits weak but detectable activity against JMJD2E (IC50=4,500±1,100 nM), a Jumonji protein demethylase, and DNA methyltransferase DNMT1 (IC50=107,000±6,000 nM), its selectivity for G9a and GLP over JMJD2E exceeds 200-fold, and its selectivity over DNMT1 exceeds 5,000-fold [1]. UNC0638 is a small molecule that selectively inhibits the enzymatic activity of histone methyltransferase EHMT, consequently reducing H3K9 dimethylation (H3K9me2) levels in cells [2].
体外研究
UNC0638 is an inhibitor of G9a and GLP with remarkable potency and selectivity across a wide array of epigenetic and non-epigenetic targets. The Ki value of UNC0638 is determined to be 3.0±0.05 nM (n=2), consistent with the Morrison Ki value of 3.7±0.2 nM (n=3). UNC0638 exhibits notable selectivity over various epigenetic targets, including H3K9 (SUV39H1 and SUV39H2), H3K27 (EZH2), H3K4 (SETD7, MLL, and SMYD3), H3K79 (DOT1L), and H4K20 (SETD8) methyltransferases, as well as PRDM1, PRDM10, and PRDM12. Additionally, UNC0638 displays inactivity against protein arginine methyltransferases PRMT1 and PRMT3, and HTATIP, a histone acetyltransferase. Although UNC0638 exhibits weak but detectable activity against JMJD2E (IC50=4,500±1,100 nM), a Jumonji protein demethylase, and DNA methyltransferase DNMT1 (IC50=107,000±6,000 nM), its selectivity for G9a and GLP over JMJD2E exceeds 200-fold, and its selectivity over DNMT1 exceeds 5,000-fold [1].
UNC0638 is a small molecule that selectively inhibits the enzymatic activity of histone methyltransferase EHMT, consequently reducing H3K9 dimethylation (H3K9me2) levels in cells [2].
作用机制
UNC0638 is a substrate-competitive inhibitor, but does not compete with the cofactor SAM, which is distinguished with the other inhibitor. [2]
UNC0638 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
22Rv1 cells
Function assay
Inhibition of G9a in human 22Rv1 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay, IC50=0.048 μM
21780790
H1299 cells
0.25 uM
Function assay
24 h
Inhibition of G9a expressed in H1299 cells assessed as inhibition of dimethylation of p53 at lys 373 at 0.25 uM after 24 hrs by Western blot analysis
21780790
HCT116 cells
Function assay
Inhibition of G9a in human HCT116 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay, IC50=0.21 μM
21780790
IMR90 cells
Function assay
Inhibition of G9a in human IMR90 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay, IC50=0.12 μM
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