Home>>Signaling Pathways>> Chromatin/Epigenetics>> Histone Methyltransferase>>EPZ-6438
EPZ-6438 Catalog No.GC14062

A EZH2 inhibitor,potent and selective

Size Price Stock Qty
10mM (in 1mL DMSO)
$55.00
In stock
5mg
$41.00
In stock
20mg
$78.00
In stock
50mg
$108.00
In stock
100mg
$181.00
In stock
500mg
$639.00
In stock
1g
$989.00
In stock
3g
$1,751.00
In stock

Customer Review

Based on customer reviews.

Tel: (626) 353-8530 Email: sales@glpbio.com

Sample solution is provided at 25 µL, 10mM.

Product Citations

Quality Control

Quality Control & SDS

View current batch:

Protocol

细胞实验[1]:

细胞系

SMARCB1 缺陷的 MRT 细胞

制备方法

溶解度有限。获得更高浓度的一般提示:请将试管在 37 ℃ 下加热 10 分钟和/或在超声波浴中摇晃一会儿。原液可在-20℃以下保存数月。

反应条件

4-7天

应用

EPZ-6438 以浓度依赖性方式诱导全局 H3K27Me3 水平降低。此外,EPZ-6438 具有显着的抗增殖作用,因为 IC50 值在纳摩尔范围内。EPZ-6438 的处理导致 CD133、DOCK4 和 PTPRK 的表达,并以时间依赖性方式上调 CDKN1A、CDKN2A 和 BIN1。

动物实验[2]:

动物模型

携带 EZH2 突变淋巴瘤异种移植物的 SCID 小鼠。

剂型

每天 3 次,每 8 小时一次,每天 2 次,每 12 小时一次,或每天一次,连续 7 或 28 天通过口服强饲法给药。

应用

EPZ-6438 剂量依赖性地导致肿瘤 H3K27Me3 水平降低 (EC50 =23 nmol/L)。EPZ-6438 还以剂量依赖性方式显示出显着的抗肿瘤作用,包括 7 天开/7 天停和 21 天开/7 天停计划的 2 个周期。除最低组外,所有 EPZ-6438 剂量组均导致肿瘤完全消退。

其他注意事项

请在室内测试所有化合物的溶解度,实际溶解度可能与理论值略有不同。这是由实验系统错误引起的,属于正常现象。

参考:

1. Knutson SK、Warholic NM、Wigle TJ 等。通过抑制甲基转移酶 EZH2 在遗传改变的恶性横纹肌瘤中实现持久的肿瘤消退。Proc Natl Acad Sci US A. 2013 年 5 月 7 日;110(19):7922-7。

2. Knutson SK、Kawano S、Minoshima Y 等人。EPZ-6438 选择性抑制 EZH2 可在 EZH2 突变型非霍奇金淋巴瘤中产生有效的抗肿瘤活性。摩尔癌症治疗。2014 年 4 月;13(4):842-54。

Chemical Properties

Cas No. 1403254-99-8 SDF
Synonyms E-7438Tazemetostat
Chemical Name N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl(oxan-4-yl)amino]-2-methyl-5-[4-(morpholin-4-ylmethyl)phenyl]benzamide
Canonical SMILES CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C4=CC=C(C=C4)CN5CCOCC5
Formula C34H44N4O4 M.Wt 572.74
Solubility ≥ 28.637mg/mL in DMSO Storage Desiccate at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

Background

EPZ-6438 is a potent and bio-available inhibitor of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2) catalyzing the methylation of lysine 27 of histone H3 (H3K27), that inhibits the activity of human PRC2-containing wild-type EZH2 with a value of inhibition constant Ki of 2.5 nM. EPZ-6438 competitively binds to the S-adenosylmethionine (SAM) binding site of EZH2 and also non-competitively binds to the binding sites of peptide or nucleosome substrate. EPZ-6438 selectively inhibits EZH2 with selectivity 35-fold greater than EZH1. Study results have suggested that EPZ-6438 exhibits dramatic and permanent anti-tumor activity in MRT models through synergistic effects of EPZ-6438-mediated EZH2 inhibition on several cancer pathways.

Reference

[1].Sarah K. Knutson1, Natalie M. Warholic, Tim J. Wigle, Christine R. Klaus, Christina J. Allain, Alejandra Raimondi, Margaret Porter Scott, Richard Chesworth, Mikel P. Moyer, Robert A. Copeland, Victoria M. Richon, Roy M. Pollock, Kevin W. Kuntz, and Heike Keilhack. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. PNAS 2013; 110(19): 7922-7927