Tazemetostat (EPZ-6438)

別名：E7438

製品コード：S7128 純度：99.90%

Tazemetostat (EPZ-6438, E7438) is a potent, and selective EZH2 inhibitor with K_i and IC50 of 2.5 nM and 11 nM in cell-free assays, exhibiting a 35-fold selectivity versus EZH1 and >4,500-fold selectivity relative to 14 other HMTs.

CAS No. 1403254-99-8

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 41500	国内在庫あり
10mg	JPY 29500	国内在庫あり
50mg	JPY 100500	国内在庫あり
1g	JPY 295500	国内在庫あり

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（144）

製品安全説明書

現在のバッチを見る：純度： 99.90%

99.90

Tazemetostat (EPZ-6438)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
Pfeiffer	Antitumor assay	100 mg/kg	20 days	Antitumor activity against human Pfeiffer cells xenografted in athymic nude mouse assessed as tumor growth inhibition at 100 mg/kg, po qd administered for 20 days measured twice per week	29456795
human HeLa cells	Function assay		72 h	Inhibition of EZH2 in human HeLa cells assessed as reduction in H3K27me3 levels incubated for 72 hrs by ELISA method, IC50=0.02 μM.	26189078
Sf9	Function assay		2 h	Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fl, IC50 = 0.004 μM.	29456795
KARPAS422	Antiproliferative activity assay		3 to 4 days up to 14 days	Antiproliferative activity against human KARPAS422 cells harboring monoallelic Y641N EZH2 mutation assessed as reduction in cell viability measured every 3 to 4 days up to 14 days by Beckman Coulter-based method, IC50 = 0.012 μM.	28092155
Pfeiffer	Cytotoxicity assay		5 days	Cytotoxicity against human Pfeiffer cells assessed as decrease in cell viability after 5 days by CellTiter-Glo reagent based luminescence assay, IC50 = 0.038 μM.	29456795
G401	Function assay		48 h	Inhibition of EED in human G401 cells assessed as reduction in global H3K27me3 level after 48 hrs by ELISA, IC50 = 0.04 μM.	28092155
G401	Function assay		4 h	Inhibition of methyltransferase activity of EZH2 in human G401 cells assessed as H3K27 trimethylation after 4 hrs by ELISA, EC50 = 0.2 μM.	26769278
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生物活性

製品説明

特性

Orally bioavailable EZH2-selective inhibitor for both wild-type and mutant. Currently being tested in Phase II clinical trials for treatment of Diffuse Large B Cell Lymphoma.

Targets

EZH2 ^[1]
(Cell-free assay)

2.5 nM(Ki)

In Vitro
In vitro	EPZ-6438 concentration-dependently reduces global H3K27Me3 levels in wild-type or SMARCB1 mutant cells, and induces strong antiproliferative effects with IC50 ranging from 32 nM to 1000 nM in SMARCB1-deleted MRT cell lines. EPZ-6438 induces gene expression of neuronal differentiation and cell cycle inhibition, while inhibtis expression of Hedgehog pathway genes, MYC and EZH2. ^[1] The antiproliferative effect of EPZ-6438 is enhanced by either NSC-9900 or Hexadecadrol in several EZH2 mutant lymphoma cell lines. ^[2]
Kinase Assay	Biochemical Methods
Kinase Assay	EPZ-6438 is incubated for 30 min with 40 μL per well of 5 nM PRC2 (final assay concentration in 50 μL is 4 nM ) in 1X assay buffer (20 mM Bicine [pH 7.6], 0.002% Tween-20, 0.005% Bovine Skin Gelatin and 0.5 mM DTT). 10 μL per well of substrate mix comprising assay buffer 3 H-SAM, unlabeled SAM, and peptide representing histone H3 residues 21-44 containing C-terminal biotin (appended to a C-terminal amide-capped lysine) are added to initiate the reaction (both substrates are present in the final reaction mixture at their respective Km values, an assay format referred to as ‘‘balanced conditions’’. The final concentrations of substrates and methylation state of the substrate peptide are indicated for each enzyme Reactions are incubated for 90 min at room temperature and quenched with 10 μL per well of 600 μM unlabeled SAM, Then transferred to a 384-well flashplate and washed after 30 min.
細胞実験	細胞株	Mutant cell lines (G401, A204, G402, KYM-1), Wild type cell line (RD, 293, SJCRH30)
	濃度	~10 μM
	反応時間	7 days
	実験の流れ	For the adherent cell line proliferation assays, plating densities for each cell line are determined based on growth curves (measured by ATP content) and density over a 7-d time course. On the day before compound treatment, cells are plated in either 96-well plates in triplicate (for the day 0–7 time course) or 6-well plates (for replating on day 7 for the remainder of the time course). On day 0, cells are either untreated, DMSO-treated, or treated with EPZ-6438 starting at 10 µM and decreasing in either threefold or fourfold dilutions. Plates are read on day 0, day 4, and day 7 using Cell Titer Glo, with compound/media being replenished on day 4. On day 7, the six-well plates are trypsinized, centrifuged, and resuspended in fresh media for counting by Vi-Cell. Cells from each treatment are replated at the original density in 96-well plates in triplicate. Cells are allowed to adhere to the plate overnight, and cells are treated as on day 0. On days 7, 11, and 14, plates are read using Cell Titer Glo, with compound/media being replenished on day 11. Averages of triplicates are used to plot proliferation over the time course, and calculate IC50 values. For cell cycle and apoptosis, G401 and RD cells are plated in 15-cm dishes in duplicate at a density of 1 × 106 cells per plate. Cells are incubated with EPZ-6438 at 1 µM, in a total of 25 mL, over a course of 14 d, with cells being split back to original plating density on day 4, 7, and 11. Cell cycle analysis and TUNEL assay are performed using a Guava flow cytometer, following the manufacturer’s protocol.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	H3K27me3 EZH2		29670078
	Immunofluorescence	HP1/Rap1		29670078

In Vivo
In Vivo	In SCID mice bearing s.c. G401 xenografts, EPZ-6438 induces tumor stasis during the administration period and produces a significant tumor growth delay with minimal effect on body weight. ^[1]
動物実験	動物モデル	SCID mice bearing s.c. G401 xenografts.
	投与量	~500 mg/kg
	投与経路	Oral administration

参考
[1] Knutson SK, et al. Proc Natl Acad Sci U S A. 2013, 110(19), 7922-7927. [2] Johnston LD, et al. ASH Annual Meeting Abstracts. 2013.

参考

化学情報

分子量	572.74	化学式	C₃₄H₄₄N₄O₄
CAS No.	1403254-99-8	SDF	Download Tazemetostat (EPZ-6438) SDFをダウンロードする
Smiles	CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C4=CC=C(C=C4)CN5CCOCC5
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 : 100 mg/mL ( (174.59 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。

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

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よくある質問（FAQ）

質問1:
Could you please help test the formulation of S7128 for in vivo studies?

回答
We've tried some vehicles for S7128 EPZ-6438, and found it can be dissolved in 2% DMSO+30% PEG 300+5% Tween+ddH2O at 5 mg/ml as a clear solution. S7128 dissolved in 5% DMSO+0.5% CMC Na at 15 mg/ml is a suspension for oral gavage.

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