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EPZ5676

Catalog No.GC12932

A highly potent DOT1L inhibitor

Products are for research use only. Not for human use. We do not sell to patients.

EPZ5676 Chemical Structure

Cas No.: 1380288-87-8

Size Price Stock Qty
10mM (in 1mL DMSO)
$148.00
In stock
2mg
$70.00
In stock
5mg
$117.00
In stock
10mg
$179.00
In stock
25mg
$342.00
In stock
50mg
$643.00
In stock
100mg
$990.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 1 publications

Product Documents

Quality Control & SDS

View current batch:

Protocol

Kinase experiment [1]:

Biochemical enzyme inhibition assays

The enzyme inhibition constant (Ki) value for EPZ5676 was determined by fitting inhibition data to the Morrison quadratic equation. Residence time for EPZ5676 was calculated as the reciprocal of the enzymatic-ligand dissociation rate, determined by surface plasmon resonance.

Cell experiment [1]:

Cell lines

MV4-11 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months.

Reaction Conditions

0.0005 ~ 10 μM; 14 days

Applications

EPZ5676 potently inhibited MV4-11 cell proliferation with an IC50 value of 3.5 nM. Antiproliferative activity was realized after 4 days and was most clear after 7 days of EPZ-5676 treatment.

Animal experiment [1]:

Animal models

Nude rats bearing MV4-11 xenografts

Dosage form

35, 67 or 70 mg/kg/day; i.v.; for 21 days

Applications

In nude rats bearing MV4-11 xenografts, EPZ5676 caused complete tumor regressions that were sustained well beyond the compound infusion period with no significant weight loss or signs of toxicity.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, Boriack-Sjodin PA, Allain CJ, Klaus CR, Raimondi A, Scott MP, Waters NJ, Chesworth R, Moyer MP, Copeland RA, Richon VM, Pollock RM. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood. 2013 Aug 8;122(6):1017-1025.

Background

EPZ5676 is a potent inhibitor of DOT1L histone methyltransferase, according to X-ray crystallographic analysis, that occupies the S-adenosyl methionine (SAM) binding pocket of DOT1L and induces conformational changes in DOT1L resulting in the opening of a hydrophobic pocket beyond the amino acid portion of SAM. EPZ5676 selectively inhibits DOTIL with a value of 50% inhibition concentration IC50 of 0.8 nM, which is 37000-fold greater in selectivity than other methyltransferases, including CARM1, EHMT1/2, EZH1/2, PRMT1/2/5/6/8, SETD7, SMYD2/3, and WHSC1/1L1. EPZ5676 has been investigated for the treatment of MLL-rearranged leukemia in multiple studies where results have shown that EPZ5676 inhibits H3K79 methylation and the expression of MLL-fusion target gene and potently kills acute leukemia cell lines bearing MLL translocation.

Reference

[1].Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, Boriack-Sjodin PA, Allain CJ, Klaus CR, Raimondi A, Scott MP, Waters NJ, Chesworth R, Moyer MP, Copeland RA, Richon VM, Pollock RM. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood. 2013 Aug 8;122(6):1017-1025.

Chemical Properties

Cas No. 1380288-87-8 SDF
Chemical Name (2R,3S,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[3-[2-(6-tert-butyl-1H-benzimidazol-2-yl)ethyl]cyclobutyl]-propan-2-ylamino]methyl]oxolane-3,4-diol
Canonical SMILES CC(C)N(CC1C(C(C(O1)N2C=NC3=C2N=CN=C3N)O)O)C4CC(C4)CCC5=NC6=C(N5)C=C(C=C6)C(C)(C)C
Formula C30H42N8O3 M.Wt 562.71
Solubility ≥ 28.15 mg/mL in DMSO, ≥ 50.3 mg/mL in EtOH with ultrasonic Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 1.7771 mL 8.8856 mL 17.7711 mL
5 mM 0.3554 mL 1.7771 mL 3.5542 mL
10 mM 0.1777 mL 0.8886 mL 1.7771 mL
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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.
3. All of the above co-solvents are available for purchase on the GlpBio website.

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Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

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