UNC0638

G9a:<15 nM|GLP:19 nM

UNC0638是一种针对G9a和GLP具有高选择性、高渗透性的化学探针，其毒性/功能比率大于100，相较于BIX01294的小于6。它是针对G9a和GLP的选择性抑制剂，在广泛的表观遗传及非表观遗传靶点上展现出优越的选择性。UNC0638对SET7/9（一种H3K4 HMTase）、SET8（一种H4K20 HMTase）、PRMT3和SUV39H2的选择性超过10,000倍。在MDA-MB-231细胞中，48小时的UNC0638处理以浓度依赖的方式降低H3K9me2的水平，IC50为81 nM。UNC0638对多种细胞系的处理降低了全球H3K9me2水平，相当于对G9a和GLP进行小发夹RNA敲减的水平，同时UNC0638的功能效力与其毒性之间有着明显的分离。此外，UNC0638显著降低了MCF7细胞的克隆形成能力，在已知G9a调控的内源基因的启动子处降低H3K9me2的丰度，并不成比例地影响了编码微RNA的几个基因组位点。在小鼠胚胎干细胞中，UNC0638以浓度依赖的方式重新激活G9a沉默的基因和一种逆转录病毒报告基因，而不促进分化。[1]

DMSO:93 mg/mL (182.4 mM);Ethanol:93 mg/mL (182.4 mM);H2O:6 mg/mL (11.77 mM)

UNC0638 is dissolved in deuterated DMSO (10 mM) and deuterated Water (90:10 ratio)[1]. MDA-MB-231, PC3, HCT116 cells are cultured in RPMI with 10% FBS, 22RV1 cells in alphaMEM and 10% FBS, MCF7 and IMR90 cells in DMEM with 10% FBS. Cells are grown in the presence or absence of UNC0638 (10 nM, 100 nM, 1 μM, 10 μM, and 100 μM ) for stated amount of time. The media is removed and replaced with DMEM 10% FBS without phenol red supplemented with 1 mg/mL of MTT and incubated for 1-2 h. Live cells reduce yellow MTT to purple formazan. The resulting formazan is solubilized in acidified isopropanol and 1% Triton and absorbance measured at 570 nm, corrected for 650 nm background[1].