product name C646
Description: C646 is a potent inhibitor for histone acetyltransferase, and inhibits p300 with a Ki of 400 nM in a cell-free assay. Preferentially selective for p300 versus other acetyltransferases. C646 induces cell cycle arrest and apoptosis selectively in AML1-ETO-positive AML cells. C646 reverses epithelial to mesenchymal transition of human peritoneal mesothelial cells via blocking TGF-β1/Smad3 signaling pathway in vitro.
References: Mol Cancer Ther. 2011 Sep;10(9):1644-55; J Neurosci. 2011 May 18;31(20):7486-91.
445.42
Formula
C24H19N3O6
CAS No.
328968-36-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 13 mg/mL (29.2 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
5% DMSO+30% PEG 300+ddH2O: 1 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19428028
| In Vitro |
In vitro activity: C646 is an inhibitor for histone acetyltransferase, inhibits p300 with a Ki of 400 nM and is selective versus other acetyltransferases. C646 produces 86% inhibition of p300 in vitro at 10 μM. C646 is a classical reversible p300 inhibitor. C646 treatment (25μM) reduces histone H3 and H4 acetylation levels and abrogates TSA-induced acetylation in cells. C646 (20μM) induces apoptosis in androgen-sensitive and castration-resistant prostate cancer cell lines by interfering with AR and NF-kB pathways. C646 blocks dynamic acetylation of H3K4me3 globally in mouse and fly cells, and locally across the promoter and start-site of inducible genes in the mouse, thereby disrupting RNA polymerase II association and the activation of these genes Kinase 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, 80μM EDTA, 40μg/ml BSA, 100μM 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. Cell Assay: 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. |
|---|---|
| In Vivo | C646 infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. C646 attenuates mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord. |
| Animal model | Mouse model |
| Formulation & Dosage | Dissolved in 10% DMSO; 2×0.75 μl injection volume in each case, 1.5 μg, administered over 2 min; infusion into ILPFC |
| References | Mol Cancer Ther. 2011 Sep;10(9):1644-55; J Neurosci. 2011 May 18;31(20):7486-91. |
