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C646

Name: C646
Brand: Selleck Chemicals
SKU: S7152
Rating: 5 (113 reviews)

Catalog No.S7152 Purity:99.77%

C646 is an inhibitor for histone acetyltransferase, and inhibits p300 with a K_i 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

CAS No. 328968-36-1

Purity & Quality Control

Batch: Purity: 99.77%

99.77

C646 Related Products

Related Targets	HAT MYST GNAT p300/CBP	Click to Expand
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Related Compound Libraries	Kinase Inhibitor Library FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Highly Selective Inhibitor Library	Click to Expand

Signaling Pathway

Histone Acetyltransferase Signaling Pathway

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	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
Click to View More Cell Line Experimental Data

Biological Activity

Description

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 K_i 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
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 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

References

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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)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

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

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.000mg/ml (2.25mM)	Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

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.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

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

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

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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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