1. Epigenetics
  2. Histone Methyltransferase

EPZ-5676 (Synonyms: Pinometostat)

Cat. No.: HY-15593 Purity: 99.75%
Data Sheet SDS Handling Instructions

EPZ-5676 is a potent and selective aminonucleoside inhibitor of DOT1L histone methyltransferase with Ki of < 80 pM, demonstrating > 37,000-fold selectivity against all other PMTs tested, and inhibits H3K79 methylation in tumor.

For research use only. We do not sell to patients.
EPZ-5676 Chemical Structure

EPZ-5676 Chemical Structure

CAS No. : 1380288-87-8

Size Price Stock Quantity
10 mM * 1 mL in DMSO $149 In-stock
5 mg $120 In-stock
10 mg $160 In-stock
50 mg $580 In-stock
100 mg   Get quote  
200 mg   Get quote  

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Customer Review

    EPZ-5676 purchased from MCE. Usage Cited in: BMC Cancer. 2016 Aug 31;16:700.

    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.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    EPZ-5676 is a potent and selective aminonucleoside inhibitor of DOT1L histone methyltransferase with Ki of < 80 pM, demonstrating > 37,000-fold selectivity against all other PMTs tested, and inhibits H3K79 methylation in tumor.

    IC50 & Target

    Ki: < 80 pM (DOT1L histone methyltransferase)

    In Vitro

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

    In Vivo

    EPZ-5676 (70 mg/kg, i.p.) causes complete and sustained regression in a rat xenograft model of MLL-rearranged leukemia. 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].

    Clinical Trial
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    References
    Preparing Stock Solutions
    Concentration Volume 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
    10 mM 0.1777 mL 0.8886 mL 1.7771 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [1]

    EPZ-5676 is dissolved in DMSO.

    To analyse inhibition of histone methylation in MV4-11 cells following EPZ-5676 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 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]

    EPZ-5676 is dissolved in 10% ethanol in saline.

    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 EPZ-5676 when tumor volumes reache approximately 100 mma3. EPZ-5676 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
    Molecular Weight

    562.71

    Formula

    C₃₀H₄₂N₈O₃

    CAS No.

    1380288-87-8

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 47.8 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Inquiry Information

    Product Name:
    EPZ-5676
    Cat. No.:
    HY-15593
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