EPZ020411 hydrochloride is a selective and potent small molecule PRMT6 inhibitor with an IC50 value of 10 nM.

PRMT1:119 nM, PRMT6:10 nM, PRMT8:223 nM

EPZ020411处理导致A375人类黑色素瘤细胞外源过表达PRMT6时H3R2甲基化水平呈剂量依赖性下降（IC50=0.637±0.241 μM）。EPZ020411对PRMT6/8/1的选择性超过100倍，相较于包括PRMT3、PRMT4、PRMT5和PRMT7在内的其他组蛋白甲基转移酶，在生化检测中显示出极高的选择性。该化合物在平行人工膜渗透实验中显示出较差的渗透性[1]。

EPZ020411在大鼠体内通过皮下给药显示了良好的生物利用度。雄性Sprague-Dawley大鼠通过静脉注射单次给予EPZ020411 1 mg/kg，显示出中等的清除率(CL)为19.7±1.0 mL/min/kg，稳态分布容积(Vss)为11.1±1.6 L/kg，相当于平均终末半衰期(t1/2)为8.54±1.43小时。在5 mg/kg皮下给药后，观察到65.6 ± 4.3%的良好生物利用度，导致EPZ020411未结合血浆浓度超过PRMT6生化IC50的时间超过12小时[1]。

Cell lines: A375 cells. Concentrations: 0-20 μM. Incubation Time: 48 h. Method: A375 (CRL-1619) cells are cultured in DMEM with 10% (vol/vol) FBS. PRMT6 is cloned into EcoRI and BamHI sites of a pcDNA4 HisMAX_A plasmid. According to procedures recommended by the manufacturer, transfection of his-tagged PRMT6 or vector control is carried out using Lipofectamine LTX and Plus reagent . Cells are seeded at 200,000 cells/well in 6-well plates. The second day, the cells are concurrently transfected and treated with compound in 0.25% DMSO. Cells are incubated in the presence compound at 20 μM and collected after 48 hours treatment.

Animal Models: SD rats. Dosages: 1 mg/kg. Administration: i.v..