2. Epigenetics
  3. Histone Methyltransferase
  4. Pinometostat

Pinometostat  (Synonyms: EPZ-5676)

Cat. No.: HY-15593 Purity: 99.93%
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Pinometostat (EPZ-5676) is a potent DOT1L histone methyltransferase inhibitor with a Ki of 80 pM.

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

Pinometostat Chemical Structure

Pinometostat Chemical Structure

CAS No. : 1380288-87-8

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 87 In-stock
Solution
10 mM * 1 mL in DMSO USD 87 In-stock
Solid
1 mg USD 28 In-stock
5 mg USD 70 In-stock
10 mg USD 100 In-stock
25 mg USD 210 In-stock
50 mg USD 360 In-stock
100 mg USD 600 In-stock
200 mg   Get quote  
500 mg   Get quote  

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This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 23 publication(s) in Google Scholar

Pinometostat Related Antibodies

Top Publications Citing Use of Products

    Pinometostat purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2018 Jan 26;9(2):129.  [Abstract]

    The effects of treatment with the indicated epigenetic inhibitors on cleaved PARP (Clv-PARP) expression in both PC9/ER and HCC827/ER cells. β-actin is used as a loading control.

    Pinometostat purchased from MedChemExpress. Usage Cited in: BMC Cancer. 2016 Aug 31;16:700.  [Abstract]

    Pharmacological inhibition of DOT1L induces E-cadherin and CD24 expression in MDA-MB-231 in vitro. Cells are treated with dose effects of EPZ-5676 (0.1 μM, 1 μM, 10 μM) or 0.1 % DMSO for the indicated days, followed by mRNA extraction and RT-qPCR with specific primers.

    View All Histone Methyltransferase Isoform Specific Products:

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

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Pinometostat (EPZ-5676) is a potent DOT1L histone methyltransferase inhibitor with a Ki of 80 pM.

    IC50 & Target

    DOT1L

     

    In Vitro

    Pinometostat (EPZ-5676) inhibits H3K79me2 with IC50 values of 3 nM and 5 nM in MV4-11 and HL60 cells, respectively. Pinometostat (EPZ-5676) is a potent inhibitor of MV4-11 proliferation with an IC50 value of 3.5 nM[1]. Pinometostat (EPZ-5676) induces a synergistic and durable antiproliferative effect, increases expression of differentiation markers and apoptosis as single agent, and demonstrates combination benefit in combination with AML standard of care drugs in MLL-r cells[2].

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

    Pinometostat Related Antibodies
    In Vivo

    Pinometostat (EPZ-5676) (70 mg/kg, i.p.) causes complete and sustained regression in a rat xenograft model of MLL-rearranged leukemia. Pinometostat (EPZ-5676) (70, 35 mg/kg, i.v.) reduces HOXA9 and MEIS1 mRNA levels of tumors taken from rats, and reduces MLL-fusion target gene expression in vivo[1].

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

    562.71

    Formula

    C30H42N8O3
    CAS No.
    Appearance

    Solid

    Color

    White to light yellow

    SMILES

    NC1=NC=NC2=C1N=CN2[C@H]3[C@H](O)[C@H](O)[C@@H](CN([C@@H]4C[C@H](CCC5=NC6=C(C=CC(C(C)(C)C)=C6)N5)C4)C(C)C)O3
    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
    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (177.71 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Ethanol : 100 mg/mL (177.71 mM; Need ultrasonic)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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
    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, 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

    • Dilution Calculator

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

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

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    Volume (start)

    V1

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    Concentration (final)

    C2

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    In Vivo:

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

    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 (4.44 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.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

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

      Solubility: ≥ 2.5 mg/mL (4.44 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.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    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).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    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).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.99%

    COA (250 KB) HNMR (316 KB) LCMS (94 KB)

    Handling Instructions (2659 KB)
    References
    Cell Assay
    [1]

    To analyse inhibition of histone methylation in MV4-11 cells following Pinometostat treatment, extracted histones (400 ng) are fractionated on a 10-20% Tris HCl gels with Tris-Glycine SDS running buffer under denaturing conditions and transferred to nitrocellulose filters. Filters are cut into strips and incubated for 1 hour in blocking buffer at room temperature (RT) and then incubated overnight at 4°C in blocking buffer. Filters are washed 3 times for 5 minutes with wash buffer (Phosphate buffered saline (PBS) including 0.01% Tween 20 (PBST)) and incubated with infrared tagged secondary antibody at RT for 1 hour. Filters are washed in PBST and reprobed for 1 hour at RT with the appropriate total histone antibody control (mouse anti-histone H3 (1:20,000), CST 3638, or mouse anti-histone H4 (1:10,000), CST 2935). Filters are washed again in PBST and incubated with infrared tagged secondary antibody (IRDye 800Cw donkey-anti-mouse IgG (1:20,000), Li-Cor 926-32212) at RT for 1 hour. After a final ish in PBST, filters are scanned using the Odyssey infared imager (Li-cor). To analyse inhibition of H3K79 methylation in peripheral blood mononuclear cells (PBMCs) from rats dosed with Pinometostat (EPZ-5676), 20 μL of PBMC whole cell lysate is fractionated on denaturing gels and analysed by immunoblotting with antibodies to H3K79me2 or total H3. Signal intensities specific for the H3K79me2 antibody and total histone H3 control antibody are quantified using Odyssey software. The H3K79me2 signal intensity is normalized by dividing it by the total histone H3 control signal intensity in the same lane.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1]

    0.2 mL of a MV4-11 cell suspension (1×107 cells) in PBS is injected subcutaneously into female athymic nude mice (Crl:NU(Ncr)-Foxn1nu). Tumors are measured by calipers and mice are randomized according to tumor size into treatment groups (n=10) before the initiation of dosing with Pinometostat (EPZ-5676) when tumor volumes reache approximately 100 mma3. Pinometostat is administered intraperitoneally three times daily for 28 days at 10 and 20 mg/kg in 10% ethanol in saline. Mice are weighed and tumors measured with calipers twice weekly until the end of the study.

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

    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, 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 / Ethanol 1 mM 1.7771 mL 8.8856 mL 17.7711 mL 44.4279 mL
    5 mM 0.3554 mL 1.7771 mL 3.5542 mL 8.8856 mL
    10 mM 0.1777 mL 0.8886 mL 1.7771 mL 4.4428 mL
    15 mM 0.1185 mL 0.5924 mL 1.1847 mL 2.9619 mL
    20 mM 0.0889 mL 0.4443 mL 0.8886 mL 2.2214 mL
    25 mM 0.0711 mL 0.3554 mL 0.7108 mL 1.7771 mL
    30 mM 0.0592 mL 0.2962 mL 0.5924 mL 1.4809 mL
    40 mM 0.0444 mL 0.2221 mL 0.4443 mL 1.1107 mL
    50 mM 0.0355 mL 0.1777 mL 0.3554 mL 0.8886 mL
    60 mM 0.0296 mL 0.1481 mL 0.2962 mL 0.7405 mL
    80 mM 0.0222 mL 0.1111 mL 0.2221 mL 0.5553 mL
    100 mM 0.0178 mL 0.0889 mL 0.1777 mL 0.4443 mL
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    Pinometostat Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    Pinometostat1380288-87-8EPZ-5676EPZ5676EPZ 5676Histone MethyltransferaseInhibitorinhibitorinhibit

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