EPZ004777 hydrochloride

Name: EPZ004777 hydrochloride
Brand: MedChemExpress
SKU: HY-15227A
Rating: 5.0 (10 reviews)

Cat. No.: HY-15227A Purity: 98.92%: Data Sheet
COA

SDS
Handling Instructions
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EPZ004777 hydrochloride is an effective and selective DOT1L inhibitor, with IC₅₀ being 0.4 nM. EPZ004777 hydrochloride reduces the levels of H3K79me2 and H3K79me1, significantly down-regulating the expression of HOXA9 and MEIS1. EPZ004777 hydrochloride selectively inhibits the proliferation of MLL rearrangement cells and promotes the differentiation and subsequent apoptosis (apoptosis) of leukemia cells. EPZ004777 hydrochloride can be used for the study of leukemia.

For research use only. We do not sell to patients.

CAS No. : 1380316-03-9

Size	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	Get quote
200 mg	Get quote

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Customer Review

Based on 10 publication(s) in Google Scholar

Other Forms of EPZ004777 hydrochloride:

EPZ004777 In-stock

10 Publications Citing Use of MCE EPZ004777 hydrochloride

Cell Proliferation/Viability Assay

In Vivo Efficacy Study

: EPZ004777 hydrochloride purchased from MedChemExpress. Usage Cited in: Oncogene. 2024 Jun;43(25):1900-1916. [Abstract]; LSCs from Atm^+/+ and Atm^−/− F2 recipients were treated with different doses of the DOT1L inhibitor (EPZ004777) for 7 days. The cell viability was then determined by the CCK8 assay.

: EPZ004777 hydrochloride purchased from MedChemExpress. Usage Cited in: Sci Adv. 2023 Jun 2;9(22):eadc9273. [Abstract]; H3K79me2 levels in HCI-H460 cells expressing WT or R231Q DOT1L after treatment with different concentrations (0.5, and 5 μM, 9 days) of DOT1Lis (SGC0946, EPZ004777, and EPZ5676)

: EPZ004777 hydrochloride purchased from MedChemExpress. Usage Cited in: Oncogenesis. 2021 Jul 12;10(7):48. [Abstract]; The indicated ovarian cancer cell lines were treated with various concentrations of DOT1L inhibitors EPZ004777 for 48 h. H3K79dimethyl marks were then measured. Histone H3 and ACTINB proteins were measured as loading controls. The results demonstrated that EPZ004777 effectively inhibited H3K79 dimethylation (H3K79me2) modification.

: EPZ004777 hydrochloride purchased from MedChemExpress. Usage Cited in: Oncogenesis. 2021 Jul 12;10(7):48. [Abstract]; The indicated ovarian cancer cell lines were treated with the DOT1L inhibitor EPZ004777 (10 µM) and SGC0946 (20 µM) for 3 days and analyzed for cell survival in MTT assays. The results showed that EPZ004777 could effectively inhibit the short-term growth of ovarian cancer cells.

: EPZ004777 hydrochloride purchased from MedChemExpress. Usage Cited in: Oncogenesis. 2021 Jul 12;10(7):48. [Abstract]; IGROV-1 cells were injected subcutaneously into the flanks of NSG mice (n = 5). The mice were treated with EPZ004777 (50 mg/kg) intraperitoneally every day and analyzed for tumor growth. Tumor sizes were measured each week and the average tumor volume is plotted (E). Representative images of the tumors from the mice after 6 weeks of EPZ004777 treatment are shown (F). The results showed that treatment with EPZ004777, a DOT1L inhibitor, elicited inhibitory effects on ovarian cancer tumor growth in vivo in xenograft models.

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•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All Histone Methyltransferase Isoform Specific Products:

View All Isoforms

EZH1 EZH2 DOT1L SMYD2 SMYD3 SUV39H2/KMT1B EHMT2/G9a/KMT1C EHMT1/GLP/KMT1D ASH1L/KMT2H SETDB1/KMT2G SETD2/KMT3A NSD2/MMSET/WHSC1 NSD3/WHSC1L1 SETD7/KMT7 SETD8/KMT5A PRMT1 PRMT3 PRMT4 PRMT5 PRMT6 PRMT7 PRMT8

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target

DOT1L

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].

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

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].

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

Molecular Weight

576.13

Formula

C₂₈H₄₂ClN₇O₄

CAS No.

1380316-03-9

Appearance

Solid

Color

Light yellow to yellow

SMILES

NC1=C2C(N([C@H]3[C@H](O)[C@H](O)[C@@H](CN(C(C)C)CCCNC(NC4=CC=C(C(C)(C)C)C=C4)=O)O3)C=C2)=NC=N1.[H]Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

Solvent & Solubility

In Vitro:

H₂O : 100 mg/mL (173.57 mM; Need ultrasonic)

DMSO : 100 mg/mL (173.57 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.7357 mL	8.6786 mL	17.3572 mL
5 mM	0.3471 mL	1.7357 mL	3.4714 mL
10 mM	0.1736 mL	0.8679 mL	1.7357 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator
Dilution Calculator

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: PBS
Solubility: 100 mg/mL (173.57 mM); Clear solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Calculation results:

Working solution concentration: mg/mL

This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).

Purity & Documentation

Purity: 98.92%

Select Batch:

Data Sheet (280 KB) SDS (252 KB)

COA (249 KB) HNMR (290 KB) LCMS (105 KB)

Handling Instructions (2659 KB)

References

[1]. Daigle SR, et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell. 2011 Jul 12;20(1):53-65. [Content Brief]

[2]. Chen L, et al. Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia. 2013 Apr;27(4):813-22. [Content Brief]

[3]. Deshpande AJ, et al. Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l.Blood. 2013 Mar 28;121(13):2533-41. [Content Brief]

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-Prkdc^scidIl2rg^tm1Wjl/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.
References	[1]. Daigle SR, et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell. 2011 Jul 12;20(1):53-65. [Content Brief] [2]. Chen L, et al. Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia. 2013 Apr;27(4):813-22. [Content Brief] [3]. Deshpande AJ, et al. Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l.Blood. 2013 Mar 28;121(13):2533-41. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

H₂O / DMSO	1 mM	1.7357 mL	8.6786 mL	17.3572 mL	43.3930 mL
	5 mM	0.3471 mL	1.7357 mL	3.4714 mL	8.6786 mL
	10 mM	0.1736 mL	0.8679 mL	1.7357 mL	4.3393 mL
	15 mM	0.1157 mL	0.5786 mL	1.1571 mL	2.8929 mL
	20 mM	0.0868 mL	0.4339 mL	0.8679 mL	2.1696 mL
	25 mM	0.0694 mL	0.3471 mL	0.6943 mL	1.7357 mL
	30 mM	0.0579 mL	0.2893 mL	0.5786 mL	1.4464 mL
	40 mM	0.0434 mL	0.2170 mL	0.4339 mL	1.0848 mL
	50 mM	0.0347 mL	0.1736 mL	0.3471 mL	0.8679 mL
	60 mM	0.0289 mL	0.1446 mL	0.2893 mL	0.7232 mL
	80 mM	0.0217 mL	0.1085 mL	0.2170 mL	0.5424 mL
	100 mM	0.0174 mL	0.0868 mL	0.1736 mL	0.4339 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.