Name: EPZ-6438 (Tazemetostat)
Brand: Selleck Chemicals
SKU: S7128
Rating: 5 (185 reviews)

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Quality Control

Batch: Purity: 99.90%

99.90

Products Often Used Together with EPZ-6438 (Tazemetostat)

UNC1999

This compound and UNC1999 treatment reduce liver steatosis in STAM non-alcoholic steatohepatitis (NASH) mice.

Lirametostat (CPI-1205)

This compound and Lirametostat are small-molecule EZH2 inhibitors that exhibit antineoplastic effects in hematologic malignancies.

Valemetostat (DS-3201)

This compound and Valemetostat are EZH2 inhibitors that induce proliferation arrest, differentiation, and apoptosis in diffuse large B-cell lymphoma (DLBCL) cells.

Related Targets	HDAC JAK BET Histone Methyltransferase PKC PARP HIF PRMT AMPK Histone Acetyltransferase
Other EZH2 Inhibitors	PF-06821497 GSK126 Tulmimetostat (CPI-0209) GSK343 EBI-2511 EZH2/HSP90-IN-29 SHR2554

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
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
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
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	572.74	Formula	C₃₄H₄₄N₄O₄	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1403254-99-8	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	E7438			Smiles	CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C4=CC=C(C=C4)CN5CCOCC5

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (174.59 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.630mg/ml (1.10mM)	Taking the 1 mL working solution as an example, add 50 μL of 12.5 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to make it clear. Volume up to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Features	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/IC₅₀/Ki	EZH2 (Cell-free assay) 2.5 nM(Ki)
In vitro	Tazemetostat (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. It induces gene expression of neuronal differentiation and cell cycle inhibition, while inhibtis expression of Hedgehog pathway genes, MYC and EZH2. The antiproliferative effect of this compound is enhanced by either NSC-9900 or Hexadecadrol in several EZH2 mutant lymphoma cell lines.
Kinase Assay	Biochemical Methods
Kinase Assay	Tazemetostat (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.
In vivo	In SCID mice bearing s.c. G401 xenografts, Tazemetostat (EPZ-6438) induces tumour stasis during the administration period and produces a significant tumour growth delay with minimal effect on body weight.
References	[1] https://pubmed.ncbi.nlm.nih.gov/23620515/ [2] https://ash.confex.com/ash/2013/webprogram/Paper61408.html

Applications

Methods	Biomarkers	Images	PMID
Western blot	EZH2 H3K27me3		26360609
Immunofluorescence	HP1/Rap1		29670078

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

Question 1:
Could you please help test the formulation of it for in vivo studies?

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

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EPZ-6438 (Tazemetostat) EZH2 inhibitor

Chemical Structure

Molecular Weight: 572.74