C646

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.

CAS No. 328968-36-1

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
10mg	JPY 22000	国内在庫あり
50mg	JPY 85500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（97）

製品安全説明書

C646関連製品

関連ターゲット	HAT MYST GNAT p300/CBP	もっと見る
関連製品	Curcumin Anacardic Acid MG149 A-485 Remodelin hydrobromide WM-1119 YF-2 CPTH2	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Bioactive Compound Library-Ⅱ	もっと見る

シグナル伝達経路

Histone Acetyltransferaseシグナル伝達経路

Histone Acetyltransferase阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
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
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
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
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
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
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
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
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
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
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
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
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
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(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
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

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.

特性

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.
細胞実験	細胞株	C3H10T1/2
	濃度	~25 μM
	反応時間	1 to 3 hr
	実験の流れ	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.
実験結果図	Methods	Biomarkers	結果図	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]
動物実験	動物モデル	mouse
	投与量	2×0.75 μl injection volume in each case, 1.5 μg, administered over 2 min
	投与経路	infusion into ILPFC

参考
[1] Bowers EM, et al. Chem Biol, 2010, 17(5), 471-482. [2] Santer FR, et al. Mol Cancer Ther, 2011, 10(9), 1644-1655. [3] Crump NT, et al. PNAS, 2011, 108(19), 7814-7819. [4] Marek R, et al. J Neurosci, 2011, 31(20), 7486-7491. [5] Zhu XY, et al. Mol Pain, 2012, 8(84) + 展開

参考

+ 展開

化学情報

分子量	445.42	化学式	C₂₄H₁₉N₃O₆
CAS No.	328968-36-1	SDF	Download C646 SDFをダウンロードする
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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 11 mg/mL ( (24.69 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):