Cat. No.: HY-15227

EPZ004777

Name: EPZ004777
Brand: MedChemExpress
SKU: HY-15227
Price: 95.00 USD
Availability: InStock
Rating: 5 (11 reviews)

11 Cited Publications

Customer Review

Based on 11 publication(s) in Google Scholar

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

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

Purity : 99.74%
CAS No.: 1338466-77-5
Formula: C₂₈H₄₁N₇O₄
Molecular Weight:539.67

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

EPZ004777 Chemical Structure

CAS No.: 1338466-77-5

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (11)
Solvent & Solubility
- In Vitro
- In Vivo
Protocols (7)
Purity & Documentation
References
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

DOT1L

All Histone Methyltransferase Isoforms :

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]
A-431	IC₅₀	264 nM Compound: EPZ004777	Downregulation of H3K79 methylation in human A-431 cells incubated for 3 to 4 days by microscopy based analysis Downregulation of H3K79 methylation in human A-431 cells incubated for 3 to 4 days by microscopy based analysis	[PMID: 23250418]
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]
MCF-10A	IC₅₀	84 nM Compound: 34, EPZ004777	Inhibition of DOT1L in human MCF10A cells assessed as reduction of H3K79 level Inhibition of DOT1L in human MCF10A cells assessed as reduction of H3K79 level	[PMID: 25406853]
MCF-10A	IC₅₀	84 nM Compound: EPZ004777	Downregulation of H3K79 methylation in human MCF-10A cells by fluorescence microscopy analysis Downregulation of H3K79 methylation in human MCF-10A cells by fluorescence microscopy analysis	[PMID: 23250418]
MOLM-13	EC₅₀	0.004 μM Compound: 22, EPZ004777	Antiproliferative activity against human MOLM13 cells containing MLL-AF9 Antiproliferative activity against human MOLM13 cells containing MLL-AF9	[PMID: 23879463]
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	EC₅₀	0.004 μM Compound: 22, EPZ004777	Antiproliferative activity against human MV4-11 cells containing MLL-AF4 Antiproliferative activity against human MV4-11 cells containing MLL-AF4	[PMID: 23879463]
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]
Sf9	IC₅₀	>20 μM Compound: EPZ004777	Inhibition of human full length PRMT5-MEP50 complex expressed in Sf9 cells Inhibition of human full length PRMT5-MEP50 complex expressed in Sf9 cells	[PMID: 25893041]
Sf9	IC₅₀	7.5 μM Compound: EPZ004777	Inhibition of human full length PRMT7 expressed in Sf9 cells Inhibition of human full length PRMT7 expressed in Sf9 cells	[PMID: 25893041]
THP-1	EC₅₀	0.004 μM Compound: 22, EPZ004777	Antiproliferative activity against human THP1 cells containing MLL-AF9 Antiproliferative activity against human THP1 cells containing MLL-AF9	[PMID: 23879463]
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]

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. Further protocols information, click here.

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.

Chemical Information

CAS No. 1338466-77-5
Appearance Solid
Molecular Weight 539.67
Formula C₂₈H₄₁N₇O₄
Color White to off-white
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
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (11)

All Cell Proliferation/Viability AssayIn Vivo Efficacy StudyWB

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Journal Impact Factor

Cancer Res

Targeting DOT1L Reactivates HERV-K to Drive Cell-Autonomous and Paracrine Senescence in Adenocarcinoma of the Esophagogastric Junction. [Abstract]

2026 Jul 15;86(14):3588-3603. PMID: 42084229
Nat Commun

Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]

2026 Feb 12;17(1):1214. PMID: 41680175
Sci Adv

Gain-of-function mutations in the catalytic domain of DOT1L promote lung cancer malignant phenotypes via the MAPK/ERK signaling pathway. [Abstract]

2023 Jun 2;9(22):eadc9273. PMID: 37256945

EPZ004777 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)
Acta Pharmacol Sin

P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib. [Abstract]

2022 Feb;43(2):457-469. PMID: 33850273
Diabetes

Molecular Mechanisms of Human Pancreatic Islet Dysfunction Under Overnutrition Metabolic Stress. [Abstract]

2025 Oct 1;74(10):1825-1838. PMID: 40773375
Oncogene

The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia. [Abstract]

2024 Jun;43(25):1900-1916. PMID: 38671157

EPZ004777 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.
Cell Syst

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations. [Abstract]

2018 Apr 25;6(4):424-443.e7. PMID: 29655704
Oncogenesis

Disruptor of telomeric silencing 1-like promotes ovarian cancer tumor growth by stimulating pro-tumorigenic metabolic pathways and blocking apoptosis. [Abstract]

2021 Jul 12;10(7):48. PMID: 34253709

EPZ004777 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 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 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.
Hematol Oncol

Establishment and characterization of a DOT1L inhibitor-sensitive human acute monocytic leukemia cell line YBT-5 with a novel KMT2A-MLLT3 fusion. [Abstract]

2019 Dec;37(5):617-625. PMID: 31701557
bioRxiv

2023 Oct 19.
Patent

US20180263995A1.

Solvent & Solubility

In Vitro:

DMSO : 66.67 mg/mL (123.54 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.8530 mL

9.2649 mL

18.5298 mL

5 mM

0.3706 mL

1.8530 mL

3.7060 mL

10 mM

0.1853 mL

0.9265 mL

1.8530 mL

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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

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

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
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: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (4.63 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (4.63 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (4.63 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

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

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

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protocols

All Molecular Biology Cell Biology Signal Pathway Related

RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (281 KB)
SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 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]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	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

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EPZ004777

Publications Citing Use of MedChemExpress (MCE) EPZ004777

All Histone Methyltransferase Isoforms