Name: C646
Brand: Selleck Chemicals
SKU: S7152
Rating: 5 (119 reviews)

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Quality Control

Batch: Purity: 99.77%

99.77

Related Targets	HDAC JAK BET Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK
Other Histone Acetyltransferase Inhibitors	PF-9363 (CTx-648) MG149 Remodelin Hydrobromide WM-1119 YF-2 EML 425 WM-3835 JQAD1 CPTH2 WM-8014

Cell Culture, Treatment & Working Concentration

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
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Chemical Information, Storage & Stability

Molecular Weight	445.42	Formula	C₂₄H₁₉N₃O₆	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	328968-36-1	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			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

Solubility

In vitro
Batch:

DMSO : 11 mg/mL (24.69 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
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.

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.

Mechanism of Action

Features	Extensively used as a pharmacologic probe in cancer cells. Potential use for prostate and lung cancers.
Targets/IC₅₀/Ki	p300/CBP (Cell-free assay) 400 nM(Ki)
In vitro	C646 is an inhibitor for histone acetyltransferase, inhibits p300 with a K_i of 400 nM and is selective versus other acetyltransferases. This compound produces 86% inhibition of p300 in vitro at 10 μM. It is a classical reversible p300 inhibitor. This chemical treatment (25μM) reduces histone H3 and H4 acetylation levels and abrogates TSA-induced acetylation in cells. It (20μM) induces apoptosis in androgen-sensitive and castration-resistant prostate cancer cell lines by interfering with AR and NF-kB pathways. This compound 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	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.
In vivo	C646 infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. This compound attenuates mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord.
References	[1] https://pubmed.ncbi.nlm.nih.gov/20534345/ [2] https://pubmed.ncbi.nlm.nih.gov/21709130/ [3] https://pubmed.ncbi.nlm.nih.gov/21518915/ [4] https://pubmed.ncbi.nlm.nih.gov/21593332/ [5] https://pubmed.ncbi.nlm.nih.gov/23176208/

Applications

Methods	Biomarkers	Images	PMID
Western blot	α-c-Myc Cyclin A1/2 / Cyclin E2 / p53 / p21 H3K27Ac		28630312
Immunofluorescence	BRD4 / p300		28630312

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

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

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

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C646 Histone Acetyltransferase p300 Inhibitor

Chemical Structure

Molecular Weight: 445.42