Home Epigenetics Histone Acetyltransferase inhibitor - Autophagy activator - Apoptosis related activator - Epigenetic Reader Domain inhibitor C646 For research use only.

C646

C646 is an 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, apoptosis and autophagy.

C646 Chemical Structure

C646 Chemical Structure

CAS No. 328968-36-1

Purity & Quality Control

C646 Related Products

Signaling Pathway

Histone Acetyltransferase Signaling Pathways

Histone Acetyltransferase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NE-4C cells Function assay 0-5 μM high glucose induced increases of H4K5ac and H4K5/8/12/16ac levels in NE-4C cells are inhibited by addition of a selective CBP/p300 inhibitor C646 in a dose-dependent way (from 0 to 5 μM) 30114346
SH-SY5Y Function assay 20 μM 24 h Co-treatment with 20 µM C646 suppressed the effect of TSA treatment on Alox15 mRNA expression by 65.7% 29235036
GES-1 Function assay 10 μM 6 h C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) 29075795
SGC-7901 Function assay 10 μM 6 h C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) 29075795
MKN45 Function assay 10 μM 6 h C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) 29075795
MGC-803 Function assay 10 μM 6 h C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) 29075795
BGC-823 Function assay 10 μM 6 h C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) 29075795
KATO III Function assay 10 μM 6 h C646 treatment significantly reduced the levels of histone H3 acetylation in both GC cells and normal gastric epithelial cells (P<0.05) 29075795
Raw246.7 Function assay 1, 5, 10, 15, 20, 25, or 30 μM 16 h results in significant inhibition of LPS and IFNγ induced NF-κB promoter activity at 15 μM or higher concentrations 26718586
WM35 Function assay 10 μM and 20 μM 24 h a dose-dependent decrease in the protein levels of cyclins A and E, accompanied by an increased expression of p53 and its downstream effector p21 23698071
1205Lu Function assay 10 μM and 20 μM 24 h a dose-dependent decrease in the protein levels of cyclins A and E, accompanied by an increased expression of p53 and its downstream effector p21 23698071
WM983B Function assay 10 μM and 20 μM 24 h a dose-dependent decrease in the protein levels of cyclins A and E, accompanied by an increased expression of p53 and its downstream effector p21 23698071
Kasumi-1 Growth inhibition assay 10, 25 and 50 μM 0, 24, 48, 72 h cellular growth and colony formation were dramatically suppressed upon C646 treatment. 23390536
SKNO-1 Growth inhibition assay 10, 25 and 50 μM 0, 24, 48, 72 h cellular growth and colony formation were dramatically suppressed upon C646 treatment. 23390536
BL21(RIL)-DE3 Function assay 10 mins Inhibition of synthetic VMA-tagged p300 (1287 to 1652 residues) (unknown origin) expressed in Escherichia coli BL21(RIL)-DE3 cells using H4-15 peptide substrate incubated for 10 mins by radiometric filter binding assay in presence of [14C]acetyl-CoA, Ki = 0.4 μM. 26701186
BL21(RIL)-DE3 Function assay 10 mins Inhibition of synthetic VMA-tagged p300 (1287 to 1652 residues) (unknown origin) expressed in Escherichia coli BL21(RIL)-DE3 cells using H4-15 peptide substrate incubated for 10 mins by radiometric filter binding assay in presence of [14C]acetyl-CoA, IC50 = 1.6 μM. 26701186
BL21-CodonPlus(DE3)-RIL Function assay 10 mins Inhibition of FLAG-tagged p300 (1195 to 1673 residues) (unknown origin) expressed in competent Escherichia coli BL21-CodonPlus(DE3)-RIL cells using histone H4 substrate incubated for 10 mins by scintillation counting method in presence of [14C]acetyl-CoA, IC50 = 9 μM. 26701186
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Biological Activity

Description C646 is an 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, apoptosis and autophagy.
Features Extensively used as a pharmacologic probe in cancer cells. Potential use for prostate and lung cancers.
Targets
p300/CBP [1]
(Cell-free assay)
400 nM(Ki)
In vitro
In vitro 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. [1] C646 (20μM) induces apoptosis in androgen-sensitive and castration-resistant prostate cancer cell lines by interfering with AR and NF-kB pathways. [2] 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. [3]
Kinase Assay 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, 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 Research Cell lines C3H10T1/2
Concentrations ~25 μM
Incubation Time 1 to 3 hr
Method 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot α-c-Myc Cyclin A1/2 / Cyclin E2 / p53 / p21 H3K27Ac 28630312
Immunofluorescence BRD4 / p300 28630312
In Vivo
In vivo C646 infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. [4] C646 attenuates mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord. [5]
Animal Research Animal Models mouse
Dosages 2×0.75 μl injection volume in each case, 1.5 μg, administered over 2 min
Administration infusion into ILPFC

Chemical Information & Solubility

Molecular Weight 445.42 Formula

C24H19N3O6
CAS No. 328968-36-1 SDF Download C646 SDF
Smiles CC1=CC(=C(C=C1C)[N+](=O)[O-])C2=CC=C(O2)C=C3C(=NN(C3=O)C4=CC=C(C=C4)C(=O)O)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 11 mg/mL ( (24.69 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
I am planning to conduct IP studies in mice, any specific vehicle that you can recommend to me?

Answer:
We found it can be dissolved in 5% DMSO+30% PEG 300+ddH2O at 1 mg/ml as a clear solution. It should be ok for i.p. injection.

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