A-366 is a highly selective peptide-competitive histone methyltransferase G9a inhibitor with IC50s of 3.3 and 38 nM for G9a and GLP, respectively.It is more than 1,000-fold selective for G9a and GLP over the other 21 methyltransferases. It is an inhibitor of the Spindlin1-H3K4me3 interaction with an IC50 of 182.6 nM.It exhibits high affinity for human H3R with a Ki value of 17 nM, and shows subtype selectivity between subgroups of the histaminergic and dopaminergic receptor families.

G9a/GLP:3.3 nM

A-366对异种移植白血病模型中肿瘤的生长产生抑制作用.

对肿瘤细胞生长而言,A-366比其他一些G9a/GLP小分子化合物抑制剂具有更少的毒性效应,而对H3K9me2的甲基化效果无差别,在体外用A-366处理各种白血病细胞株,这些肿瘤细胞将产生显著的分化和形态上的变化。

7.5× compounds are added to a 96-well PolyPlate containing 60 μL of Buffer per well with substrates CoA (200 μM), ATP (400 μM), and [14C]citrate. Reaction is started with 4 μL (300 ng/well) ACL, and the plate is incubated at 37°C for 3 h. Th

PC-3 prostate adenocarcinoma cells are incubated in triplicate with DMSO or the indicated concentrations of A-366 or UNC0638 for 72 hours. H3K9me2 levels are assessed by In-Cell Western assay. (Only for Reference)