2. Epigenetics Apoptosis
  3. Histone Methyltransferase Apoptosis
  4. EPZ004777

EPZ004777 是一种有效的选择性 DOT1L 抑制剂，IC50 为 0.4 nM。

MCE 的所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务

我们将采用定制合成服务的方式为您快速提供所需产品和技术服务

EPZ004777 Chemical Structure

EPZ004777 Chemical Structure

CAS No. : 1338466-77-5

1.  客户无需承担相应的运输费用。

2.  同一机构（单位）同一产品试用装仅限申领一次，同一机构（单位）一年内

     可免费申领三个不同产品的试用装。

3.  试用装只面向终端客户。

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ￥1187
In-stock
5 mg ￥1000
In-stock
10 mg ￥1600
In-stock
25 mg ￥3200
In-stock
50 mg ￥5000
In-stock
100 mg   询价  
200 mg   询价  

* Please select Quantity before adding items.

Customer Review

Other Forms of EPZ004777:

EPZ004777 相关抗体

Top Publications Citing Use of Products

查看 Histone Methyltransferase 亚型特异性产品:

查看所有亚型
EZH1 EZH2 DOT1L SMYD2 SMYD3 SUV39H2/KMT1B EHMT2/G9a/KMT1C EHMT1/GLP/KMT1D SETDB1/KMT2G SETD2/KMT3A NSD2/MMSET/WHSC1 SETD7/KMT7 SETD8/KMT5A PRMT1 PRMT3 PRMT4 PRMT5 PRMT6 PRMT7 PRMT8

  • 生物活性

  • 实验参考方法

  • 纯度 & 产品资料

  • 参考文献

生物活性

EPZ004777 is a potent, selective DOT1L inhibitor with an IC50 of 0.4 nM.

IC50 & Target

DOT1L

 

细胞效力
(Cellular Effect)
Cell Line Type Value Description References
697 IC50
> 10 μM
Compound: 34, EPZ004777
Cytotoxicity against human 697 cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
Cytotoxicity against human 697 cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
[PMID: 25406853]
HL-60 IC50
> 10 μM
Compound: 34, EPZ004777
Cytotoxicity against human HL60 cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
Cytotoxicity against human HL60 cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
[PMID: 25406853]
Jurkat IC50
> 10 μM
Compound: 34, EPZ004777
Cytotoxicity against human Jurkat cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
Cytotoxicity against human Jurkat cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
[PMID: 25406853]
Kasumi 1 IC50
> 10 μM
Compound: 34, EPZ004777
Cytotoxicity against human Kasumi-1 cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
Cytotoxicity against human Kasumi-1 cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
[PMID: 25406853]
MOLM-13 IC50
700 nM
Compound: 128, EPZ004777
Inhibition of DOT1L in human MOLM13 cells assessed as downregulation of HOXA9/MEIS1 mRNA expression after 6 days by real-time PCR analysis
Inhibition of DOT1L in human MOLM13 cells assessed as downregulation of HOXA9/MEIS1 mRNA expression after 6 days by real-time PCR analysis
10.1039/C1MD00199J
MV4-11 IC50
700 nM
Compound: 128, EPZ004777
Inhibition of DOT1L in human MV4-11 cells assessed as downregulation of HOXA9/MEIS1 mRNA expression after 6 days by real-time PCR analysis
Inhibition of DOT1L in human MV4-11 cells assessed as downregulation of HOXA9/MEIS1 mRNA expression after 6 days by real-time PCR analysis
10.1039/C1MD00199J
REH IC50
> 10 μM
Compound: 34, EPZ004777
Cytotoxicity against human REH cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
Cytotoxicity against human REH cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
[PMID: 25406853]
U-937 IC50
> 10 μM
Compound: 34, EPZ004777
Cytotoxicity against human U937 cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
Cytotoxicity against human U937 cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay
[PMID: 25406853]
体外研究
(In Vitro)

EPZ004777 demonstrates potent, concentration-dependent inhibition of DOT1L enzyme activity with an IC50 of 400±100 pM. EPZ004777 displays remarkable selectivity for inhibition of DOT1L over other HMTs(PRMT5, 521±137 nM; others, >50 μM). The effect of extended EPZ004777 treatment is remarkably specific for the MLL-rearranged cell lines. The number of viable MV4-11 and MOLM-13 cells is dramatically reduced by EPZ004777, whereas the growth of Jurkat cells is unaffected. A small population of MV4-11 cells remain viable in the presence of EPZ004777, but their number remain constant when growth curves are tracked over longer periods indicating that they have ceased to divide. The proliferation of MLL-AF9-transformed cells is strongly inhibited by EPZ004777 at concentrations of 3 μM or greater[1]. EPZ004777 selectively inhibits proliferation of MLL-AF10 and CALM-AF10 transformed murine bone marrow cells[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

EPZ004777 相关抗体:
体内研究
(In Vivo)

EPZ004777 is well tolerated and no overt toxicity is observed. Complete blood count analysis after 14 days of continuous exposure to EPZ004777 revealed a statistically significant increase in the total white blood cell count, which resulted from an increase in neutrophils, monocytes, and lymphocytes. EPZ004777 (50, 100, or 150 mg/mL) administration is well tolerated, and no significant weight loss is observed[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
分子量

539.67

Formula

C28H41N7O4
CAS 号
性状

固体

颜色

White to off-white

运输条件

Room temperature in continental US; may vary elsewhere.
储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
溶解性数据
细胞实验： 

DMSO 中的溶解度 : 66.67 mg/mL (123.54 mM; 超声助溶 (<60°C); 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.8530 mL 9.2649 mL 18.5298 mL
5 mM 0.3706 mL 1.8530 mL 3.7060 mL
查看完整储备液配制表

* 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C储存时，请在2年内使用， -20°C储存时，请在1年内使用。

  • 摩尔计算器

  • 稀释计算器

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

质量
=
浓度
×
体积
×
分子量 *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

浓度 (start)

C1

×
体积 (start)

V1

=
浓度 (final)

C2

×
体积 (final)

V2

动物实验：

请根据您的 实验动物和给药方式 选择适当的溶解方案。

以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：
——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 方案 一

    请依序添加每种溶剂： 10% DMSO    90% Corn Oil

    Solubility: ≥ 3 mg/mL (5.56 mM); 澄清溶液

    此方案可获得 ≥ 3 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。

    以 1 mL 工作液为例，取 100 μL 30.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

  • 方案 二

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (4.63 mM); 澄清溶液

    此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。

    生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。
动物溶解方案计算器
请输入动物实验的基本信息：

给药剂量

mg/kg

动物的平均体重

g

每只动物的给药体积

μL

动物数量

只
由于实验过程有损耗，建议您多配一只动物的量
请输入您的动物体内配方组成：
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
如果您的动物是免疫缺陷鼠或者体弱鼠，建议 DMSO 中的在最后工作液体系中的占比尽量不超过 2%。
方案所需 助溶剂 包括：DMSO， ，均可在 MCE 网站选购。 ，Tween 80，均可在 MCE 网站选购。
计算结果
工作液所需浓度 : mg/mL
储备液配制方法 : mg 药物溶于 μL  DMSO（母液浓度为 mg/mL）。
您所需的储备液浓度超过该产品的实测溶解度，以下方案仅供参考，如有需要，请与 MCE 中国技术支持联系。
动物实验体内工作液的配制方法 : 取 μL DMSO 储备液，加入 μL 。 μL ，混合均匀至澄清，再加 μL Tween 80，混合均匀至澄清，再加 μL 生理盐水。
连续给药周期超过半月以上，请谨慎选择该方案。
请确保第一步储备液溶解至澄清状态，从左到右依次添加助溶剂。您可采用超声加热 （超声清洗仪，建议频次 20-40 kHz），涡旋吹打等方式辅助溶解。
纯度 & 产品资料

纯度: 98.78%

COA (192 KB) HNMR (310 KB) RP-HPLC (248 KB) LCMS (98 KB)

产品使用指南 (1538 KB)
参考文献
Kinase Assay
[1]

Avian (chicken) erythrocyte oligonucleosomes are purified. EPZ004777 is serially diluted 3-fold in DMSO for a total of ten concentrations, beginning at 1 μM. A 1 μL aliquot of each inhibitor dilution is plated in a 384-well microtiter plate. The 100% inhibition control consisted of 2.5 μM final concentration of the product inhibitor S-adenosyl-L-homocysteine, (SAH). Compound is incubated for 30 min with 40 μL per well of 0.25 nM DOT1L(1-416) in assay buffer (20 mM TRIS [pH 8.0] 10 mM NaCl, 0.002% Tween 20, 0.005% Bovine Skin Gelatin, 100 mM KCl, and 0.5 mM DTT). 10 μL per well of substrate mix comprising assay buffer with 200 nM 3H-SAM (80 Ci/mmol), 600 nM unlabeled SAM, and 20 nM nucleosomes 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”. Reactions are incubated for 120 min and quenched with 10 μL per well of 800 μM SAM. Incorporation of radioactivity into nucleosome substrate is measured in a flashplate. IC50 values for enzymes in the histone methyltransferase panel are determined under similar balanced assay conditions with both SAM and protein/peptide substrate present at concentrations equal to their respective KM values[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay
[1]

For assessment of cell proliferation and viability in human cell lines, exponentially growing cells are plated, in triplicate, in 96-well plates at a density of 3×104 cells/well in a final volume of 150 μL. Cells are incubated in the presence of 3 μM (proliferation curve), or increasing concentrations (IC50 determination) of EPZ004777 up to 50 μM. Viable cell number is determined every 3-4 days for up to 18 days using the Guava Viacount assay and analyzed on a Guava EasyCyte Plus instrument. On days of cell counts, growth media and EPZ004777 are replaced and cells split back to a density of 5×104 cells/well. Total cell number is expressed as split-adjusted viable cells per well. For each cell line, IC50 values are determined from concentration-dependence curves at each time point using Graphpad Prism software. Experiments to determine IC50 values continued until IC50 values stabilized (day 18 for THP-1 cells, day 14 for all other cell lines)[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
Nine-week-old female nude mice (nu/nu) are injected subcutaneously with MV4-11 cells in the right flank (200 μL of a 5×107 cells/mL suspension in a 1:1 mixture of PBS and Matrigel). Mice are randomized to treatment groups when tumor sizes reached 300-400 mm3. Six mice received subcutaneous implant of osmotic pumps, containing 50 mg/mL EPZ004777 in 10% ethanol, 90% water, and five control mice received no pump implant. Six days after pump implant, animals are sacrificed and tumor samples from treated and control animals are collected for immunoblot analysis. For the disseminated leukemia model, MV4-11 cells are transduced with the pMMP-LucNeo retrovirus. Eight-week-old female NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice are purchased from Jackson Laboratories. A total of 1×107 MV4-11-LucNeo cells are injected intravenously via the lateral tail vein. Engraftment of disseminate leukemia is determined by bioluminescence imaging after injection of 75 mg/kg of D-luciferin. Animals with documented leukemia are divided into treatment groups consisting of vehicle (15% ethanol, 50% PEG300, 35% water) loaded osmotic pumps, or EPZ004777 at 50, 100, or 150 mg/mL. Osmotic pumps are replaced after one week. Irritation caused by compound precipitation is observed in the 100 and 150 mg/mL dose groups, precluding additional pump replacements. Animals are monitored daily for clinical symptoms, and are euthanized when they displayed signs of distress consistent with terminal leukemic disease. Log-rank analysis is used to determine statistical significance of the survival curves.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献

EPZ004777 相关分类

完整储备液配制表

* 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C储存时，请在2年内使用， -20°C储存时，请在1年内使用。

可选溶剂 浓度 溶剂体积 质量 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.8530 mL 9.2649 mL 18.5298 mL 46.3246 mL
5 mM 0.3706 mL 1.8530 mL 3.7060 mL 9.2649 mL
10 mM 0.1853 mL 0.9265 mL 1.8530 mL 4.6325 mL
15 mM 0.1235 mL 0.6177 mL 1.2353 mL 3.0883 mL
20 mM 0.0926 mL 0.4632 mL 0.9265 mL 2.3162 mL
25 mM 0.0741 mL 0.3706 mL 0.7412 mL 1.8530 mL
30 mM 0.0618 mL 0.3088 mL 0.6177 mL 1.5442 mL
40 mM 0.0463 mL 0.2316 mL 0.4632 mL 1.1581 mL
50 mM 0.0371 mL 0.1853 mL 0.3706 mL 0.9265 mL
60 mM 0.0309 mL 0.1544 mL 0.3088 mL 0.7721 mL
80 mM 0.0232 mL 0.1158 mL 0.2316 mL 0.5791 mL
100 mM 0.0185 mL 0.0926 mL 0.1853 mL 0.4632 mL
Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

EPZ0047771338466-77-5EPZ 004777EPZ-004777Histone MethyltransferaseApoptosisInhibitorinhibitorinhibit

您最近查看的产品:

Your information is safe with us. * Required Fields.

   产品名称：

  

* 需求量：

* 客户姓名：

 

* Email：

* 电话：

 

* 公司或机构名称：

   留言给我们：

Bulk Inquiry

Inquiry Information

产品名称：
EPZ004777
目录号：
HY-15227
需求量：

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

   产品名称：

  

* Lot #：

* 客户姓名：

 

* Email：

   电话：

 

* 部门：

* 公司或机构名称：

 

   留言给我们：

Request for HNMR Report

We have received your request and will respond to you as soon as possible.

嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z