UNC0642 is an effective and specific G9a/GLP inhibitor (IC50< 2.5 nM).

GLP:<2.5 nM, G9a:<2.5 nM

UNC0642 (Ki: 3.7±1 nM) 与肽基质竞争性抑制，并且与辅因子SAM非竞争性抑制。UNC0642对G9a和GLP的选择性超过300倍，远超过众多激酶、转运蛋白、GPCRs及离子通道。此外，UNC0642在低细胞毒性下展现出高效力，能有效降低H3K9me2标记，且在多种细胞系中具有良好的功能效力分离。

UNC0642（5 mg/kg，i.p.）在血浆中产生的最高浓度（Cmax）为947 ng/mL，面积下药物浓度时间曲线（AUC）为1265 h·ng/mL。

MDA-MB-231, PC3, and U2OS cells are treated with UNC0642 for 48 h. Cell viability assays are performed by incubating cells with 0.1 mg/mL of resazurin for 3 – 4 h. Resazurin reduction is monitored with 544 nm excitation, measuring fluorescence at 590 nm.

Mouse: Standard PK studies are performed using male Swiss albino mice. Plasma and brain concentrations are measured at 0.08, 0.25, 0.5, 1, 2, 4, 8, and 24 h following UNC0642 (5 mg/kg, i.p.). The compound concentration at each time point in plasma or brain is the average value from 3 test animals[1].