GSK343

製品コード：S7164 純度：99.95%

GSK343 is a potent and selective EZH2 inhibitor with IC50 of 4 nM in a cell-free assay, showing 60 fold selectivity against EZH1, and >1000 fold selectivity against other histone methyltransferases. GSK343 induces autophagy.

CAS No. 1346704-33-3

サイズ	価格(税別)	在庫状況
5mg	JPY 22000	国内在庫あり
25mg	JPY 55500	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

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製品安全説明書

現在のバッチを見る：純度： 99.95%

99.95

GSK343関連製品

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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 Highly Selective Inhibitor Library	もっと見る

シグナル伝達経路

Histone Methyltransferaseシグナル伝達経路

Histone Methyltransferase阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
HepG2	Function Assay	10 μM	24 h	induces autophagy	25203626
A549	Growth Inhibition Assay	0-20 μM	72 h	shows cytotoxicity in a dose-dependent manner	25203626
HepG2	Growth Inhibition Assay	0-20 μM	72 h	shows cytotoxicity in a dose-dependent manner	25203626
MDA-MB-231	Function Assay	10 μM	24 h	induces autophagy	25203626
MDA-MB-231	Function Assay	10 μM	72 h	induces LC3-II accumulation	25203626
MDA-MB-231	Function Assay	10 μM	72 h	reduces the level of H3K27-me3	25203626
MDA-MB-231	Growth Inhibition Assay	0-20 μM	72 h	shows cytotoxicity in a dose-dependent manner	25203626
2D10	Function Assay	0.25-2.0 μM	96 h	reduces total cellular trimethylated H3K27 in a time- and dose-dependent manner	26041287
A549	Function Assay	10 μM	24 h	induces autophagy	25203626
OVCAR10	Growth Inhibition Assay	1 μM	0-12 d	inhibits cell growth time dependently	23759589
UPN289	Growth Inhibition Assay	1 μM	0-12 d	inhibits cell growth time dependently	23759589
SKOV3	Growth Inhibition Assay	1 μM	0-12 d	inhibits cell growth time dependently	23759589
SKOV3	Apoptosis Assay	1 μM	4 d	induces apoptosis cultured in 3D conditions	23759589
HCC1806	Function assay		72 hrs	Inhibition of EZH2-mediated nuclear H3K27 methylation in human HCC1806 cells after 72 hrs by immunofluorescence analysis, IC50 = 0.174 μM.	24900432
LNCaP	Function assay		6 days	Inhibition of EZH2-mediated proliferation of human LNCaP cells after 6 days by chemiluminescence analysis, IC50 = 2.9 μM.	24900432
DU145	Function assay		6 days	Inhibition of EZH2-mediated proliferation of human DU145 cells after 6 days by chemiluminescence analysis	24900432
SKBR3	Function assay		6 days	Inhibition of EZH2-mediated proliferation of human SKBR3 cells after 6 days by chemiluminescence analysis	24900432
PC3	Function assay		6 days	Inhibition of EZH2-mediated proliferation of human PC3 cells after 6 days by chemiluminescence analysis	24900432
ZR-75-1	Function assay		6 days	Inhibition of EZH2-mediated proliferation of human ZR-75-1 cells after 6 days by chemiluminescence analysis	24900432
HCC180	Function assay		6 days	Inhibition of EZH2-mediated proliferation of human HCC180 cells after 6 days by chemiluminescence analysis	24900432
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生物活性

製品説明

特性

A chemical probe for the SGC epigenetics initiative. Potential use in a variety of solid tumors.

Targets

EZH2 ^[1] (Cell-free assay)	EZH1 ^[1] (Cell-free assay)
4 nM	240 nM

In Vitro
In vitro	GSK343 inhibits trimethylation of H3K27 (H3K27me3) with IC50 of 174 nM in HCC1806 breast cancer cells. GSK343 potently inhibits cell proliferation in breast cancer cells and prostate cancer cells, and the prostate cancer cell line LNCaP is the most sensitive to GSK343, with IC50 of 2.9 μM. ^[1] GSK343 significantly suppresses the growth of EOC cells cultured in 3D matrigel extracellular matrix (ECM), which mimics the tumor microenvironment in vivo. In addition, GSK343 also induces apoptosis of EOC cells in 3D and significantly inhibits the invasion of EOC cells. ^[2]
Kinase Assay	In vitro biochemical assays against histone methyltransferases
Kinase Assay	Activity against EZH2 is assessed using 5 member PRC2 complex (Flag-EZH2, EED, SUZ12, AEBP2, RbAp48). The assay protocol may be summarized as follows: 10 mM stocks of compounds are prepared from solid in 100% DMSO. An 11 point serial dilution master plate is prepared in 384 well format (1:3 dilution, columns 6 and 18 were equal volume DMSO controls) and dispensed to assay ready plates using acoustic dispensing technology to create a 100 nL stamp of compound and DMSO controls. The assay additions consisted of equal volume additions of 10 nM EZH2 and the substrate solution (5 µg/mL HeLa nucleosomes and 0.25 µM [³H]-SAM) dispensed into assay plates using a multi-drop combi dispense. Reaction plates are incubated for 1 hr and quenched with an equal volume addition of 0.5 mg/mL PS-PEI Imaging Beads (RPNQ0098) containing 0.1 mM unlabeled SAM. The plates are sealed, dark adapted for 30 minutes, and a 5 minute endpoint luminescence image is acquired using a Viewlux imager. Plate statistics such as Z’ and signal to background as well as dose response curves are analyzed using Activity BaseXE. The in vitro biochemical activity of EZH1 is assessed as part of a 5 member PRC2 complex using a 384 well SPA assay identical to EZH2. Buffer components, reagent dispensing, compound plate preparation, quench conditions and data analysis are identical for EZH1 and EZH2 with final assay concentrations of 20 nM EZH1, 5 μM/mL HeLa nucleosomes and 0.25 μM [³H]-SAM. Further data analysis, pIC50 pivots and visualizations are enabled by TIBCO Spotfire. Compounds are profiled at Reaction Biology Corp. (Malvern, PA) to assess inhibition in their panel of histone methyltransferase assays. Methyltransferase activity is assessed using HotSpot technology, a miniaturized radioisotope-based filter binding assay. Inhibitors are dissolved in dimethyl sulfoxide (DMSO) and tested at concentrations up to 100 uM with a final DMSO concentration of 2%. Buffer containing the methyltrasferase at the listed concentration and its preferred substrate as shown in the accompanying table is preincubated with compound for 10 min. Reactions are initiated by the addition of 1 uM S-adenosyl-L-[methyl-³H]methionine (SAM), allowed to incubate for 60 min at 30C followed by transfer to P81 filter-paper and PBS wash before detection.
細胞実験	細胞株	Breast cancer cell lines (HCC1806, Sk-Br-3, ZR-75-1), prostate cancer cell lines (DU145, PC3, LNCaP)
	濃度	~50 μM
	反応時間	6 days
	実験の流れ	To account for varying doubling rates among cancer cell lines, the optimal cell seeding is determined empirically for all cell lines by examining their growth in a 384-well plate over 6 days with a wide range of seeding densities. Cells are then plated at the optimal seeding density and allowed to adhere overnight. Cells are treated in duplicate with a 20-point 2-fold dilution series of compound or 0.147% DMSO (vehicle control) and incubated for 6 days at 37C in 5% CO2. Cells are then lysed with 25 μl CellTiter-Glo per well and chemiluminescence is quantified with a TECAN Safire2 microplate reader. In addition, an untreated plate of cells is harvested at the time of compound addition (T0) to quantify the starting number of cells. CTG values after 6 days of treatment were expressed as a percent of the T0 value and plotted against compound concentration. Data are fit with a 4-parameter equation to generate a concentration response curve and the concentration of compound required to inhibit 50% of growth (gIC50) is determined
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	H3K27me3 EZH2 / EED / SUZ12 N-cadherin / Vimentin / Snail / Slug / MMP2 / MMP9		29228694
	Immunofluorescence	N-cadherin / H3K27me3 / Vimentin		29228694
	Growth inhibition assay	Cell viability		26973856

In Vivo
In Vivo	GSK343, a selective EZH2 inhibitor, inhibits phagocytosis.

参考
[1] Verma SK, et al. ACS Med Chem Lett. 2012, 3, 1091-1096. [2] Amatangelo MD, et al. Cell Cycle. 2013, 12(13), 2113-2119. [3] Wang X, et al. Theranostics. 2022 Jan 31;12(5):2063-2079.

参考

化学情報

分子量	541.69	化学式	C₃₁H₃₉N₇O₂
CAS No.	1346704-33-3	SDF	Download GSK343 SDFをダウンロードする
Smiles	CCCC1=C(C(=O)NC(=C1)C)CNC(=O)C2=C3C=NN(C3=CC(=C2)C4=CC(=NC=C4)N5CCN(CC5)C)C(C)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:

Ethanol : 4 mg/mL

DMSO : 1 mg/mL ( (1.84 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

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。

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