| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
The primary target of EPZ011989 hydrochloride is Enhancer of Zeste Homolog 2 (EZH2), the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2). EZH2 is a histone-lysine N-methyltransferase that catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3). The compound binds to the SET domain of EZH2, achieving potent inhibition with a Ki value of <3 nM.
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| ln Vitro |
In vitro, EPZ011989 hydrochloride is a potent inhibitor of EZH2, effectively reducing global levels of H3K27me3 in various cancer cell lines. This inhibition leads to the derepression of genes that are silenced by PRC2, resulting in potent anti-proliferative and pro-apoptotic effects specifically in tumor cells that depend on EZH2 activity for growth. Its activity is confirmed in a range of biochemical and cellular assays.
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| ln Vivo |
In vivo, EPZ011989 hydrochloride is orally active and has shown robust anti-tumor activity in several preclinical xenograft mouse models. Oral administration of the compound leads to significant inhibition of tumor growth, which correlates with a sustained reduction of H3K27me3 levels within the tumor tissue. The compound's oral bioavailability and in vivo efficacy make it a valuable asset for validating EZH2 as a therapeutic target.
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| Enzyme Assay |
A typical cell-free assay involves incubating recombinant EZH2 (within the PRC2 complex) with a biotinylated histone H3 peptide substrate and a radiolabeled methyl donor, 3H-S-adenosyl-L-methionine (3H-SAM). Following the reaction, the peptide is captured on a streptavidin-coated plate, and the amount of 3H-methyl group transferred is measured by scintillation counting. The compound's Ki is determined by measuring inhibition at various substrate concentrations.
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| Cell Assay |
In cellular assays, cancer cell lines (e.g., lymphoma, leukemia) are treated with serial dilutions of EPZ011989 hydrochloride for 5-7 days. Cell viability is assessed using the CellTiter-Glo luminescent cell viability assay. To confirm target engagement, cellular lysates are analyzed by Western blot using an antibody specific for H3K27me3. A decrease in this histone mark indicates successful inhibition of EZH2 by the compound.
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| Animal Protocol |
For in vivo studies, immunocompromised mice are subcutaneously injected with EZH2-mutant or EZH2-dependent cancer cells (e.g., KARPAS-422, a lymphoma cell line). Once tumors are established, mice are randomized and administered EPZ011989 hydrochloride orally (p.o.) daily. Tumor volume is measured twice weekly, and at the end of the study, tumors are excised for Western blot analysis of H3K27me3 levels and for histopathological examination.
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| ADME/Pharmacokinetics |
EPZ011989 is characterized as an orally active inhibitor, indicating it has favorable drug metabolism and pharmacokinetic (DMPK) properties. It exhibits good oral bioavailability, which is essential for its in vivo efficacy. The compound is formulated for oral administration in pharmacokinetic studies, where plasma concentrations are measured over time to determine parameters such as half-life, peak concentration (Cmax), and area under the curve (AUC).
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| Toxicity/Toxicokinetics |
Specific preclinical toxicology data for EPZ011989 is not provided in the summaries. As an EZH2 inhibitor, its toxicity profile is an important aspect of its preclinical characterization. On-target effects of EZH2 inhibition may affect normal hematopoietic stem cells, leading to potential hematological side effects. However, the compound is primarily used in research to validate the therapeutic window of EZH2 inhibition in oncology.
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| References | |
| Additional Infomation |
EPZ011989 hydrochloride is an advanced tool compound from the EZH2 inhibitor class. It contains an alkyne group, making it a click chemistry reagent for copper-catalyzed azide-alkyne cycloaddition (CuAAc). This functionality allows it to be used for creating chemical probes or conjugates (e.g., for biotinylation) to study EZH2 biology. It is a research chemical and has not been approved for clinical use.
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| Molecular Formula |
C35H52CLN5O4
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|---|---|
| Molecular Weight |
642.27
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| Exact Mass |
641.37
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| CAS # |
2095432-26-9
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| Related CAS # |
EPZ011989;1598383-40-4;EPZ011989 trifluoroacetate;1598383-41-5
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| PubChem CID |
129896818
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
45
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| Complexity |
1110
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN(C1CCC(CC1)N(C)CCOC)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C#CCN4CCOCC4.Cl
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| InChi Key |
LHRBDVKQGXCMQN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C35H51N5O4.ClH/c1-7-40(30-12-10-29(11-13-30)38(5)15-18-43-6)33-23-28(9-8-14-39-16-19-44-20-17-39)22-31(27(33)4)34(41)36-24-32-25(2)21-26(3)37-35(32)42;/h21-23,29-30H,7,10-20,24H2,1-6H3,(H,36,41)(H,37,42);1H
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| Chemical Name |
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl-[4-[2-methoxyethyl(methyl)amino]cyclohexyl]amino]-2-methyl-5-(3-morpholin-4-ylprop-1-ynyl)benzamide;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~155.7 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (3.89 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (3.89 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 2.5 mg/mL (3.89 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5570 mL | 7.7849 mL | 15.5698 mL | |
| 5 mM | 0.3114 mL | 1.5570 mL | 3.1140 mL | |
| 10 mM | 0.1557 mL | 0.7785 mL | 1.5570 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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