C646 是一种竞争性组蛋白乙酰转移酶 p300选择性抑制剂，Ki值为 400 nM，对其他乙酰转移酶作用较小。

C646, a histone acetyltransferase inhibitor, inhibits p300 (Ki: 400 nM, in a cell-free assay).

在脊髓中,C646可使机械痛和热痛觉过敏衰减,且伴有对COX-2表达的抑制.C646在弱灭绝训练后,立即注入到ILPFC,对恐惧消退记忆的整合有增强作用.

在体外,C646（10 μM）可抑制86% p300。在对雄激素敏感的阉割性前列腺癌细胞系中,C646（20 μM）通过干扰AR和NF-kB通路,进而诱导细胞凋亡。C646（25 μM）可使细胞的组蛋白H3和H4乙酰化水平降低,并阻断TSA诱导的乙酰化。在小鼠细胞中,C646抑制全部H3K4me3动态乙酰化,且局部横跨启动子和诱导基因的起始位点,引起对RNA聚合酶II相互作用和这些基因激活的干扰作用。

Radioactive assay: IC50 values for the putative p300 HAT inhibitors are determined using the direct radioactive assay described above. Reactions are performed in 20 mM HEPES (pH 7.9), and contained 5 mM DTT, 80 μM EDTA, 40μg/ml BSA, 100 μM H4-15, and 5 nM p300. Putative inhibitors are added over a range of concentrations, with DMSO concentration kept constant (<5%). Reactions are incubated at 30°C for 10 min, then initiated with addition of a 1:1 mixture of 12C-acetyl-CoA and 14C-acetyl-CoA to 20 mM. After 10 min at 30°C, reactions are quenched with 14% SDS (w/v). All concentrations are screened in duplicate. Gels are run, washed, dried, and exposed to a PhosphorImager plate, and production of Ac-H4-15 quantified to obtain IC50s.

Histone acetylation assays in mouse cells. C3H10T1/2 mouse fibroblasts are grown in DMEM with 10% FCS at 37°C with 6% CO2. Confluent cultures are rendered quiescent in DMEM with 0.5% FCS for 18-20 hr prior to treatment. Cells are treated with the following compounds: TSA (10 ng/ml [33 nM]), C646 (25 μM), C37 (25 μM). Antibodies are used at the following concentrations: total H3 (1:10000; ab7834; Abcam); H4K12ac (1:2500; 06-761; Upstate). Rabbit anti-H3K9ac (1:10000) antibodies are generated in-house. Histones are isolated from cells by acid extraction, separated by SDS and acid-urea polyacrylamide gel electrophoresis and analyzed by western blotting.(Only for Reference)

328968-36-1

C24H19N3O6

445.431

DMSO:11.1 mg/mL (25 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years