1. Epigenetics
  2. Histone Methyltransferase

Pinometostat (Synonyms: EPZ-5676)

Cat. No.: HY-15593 Purity: 99.92%
Handling Instructions

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
10 mM * 1 mL in DMSO USD 178 In-stock
Estimated Time of Arrival: December 31
5 mg USD 144 In-stock
Estimated Time of Arrival: December 31
10 mg USD 192 In-stock
Estimated Time of Arrival: December 31
50 mg USD 696 In-stock
Estimated Time of Arrival: December 31
100 mg   Get quote  
200 mg   Get quote  

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Customer Review

    Pinometostat 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.

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

    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.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

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

    IC50 & Target

    Ki: < 80 pM (DOT1L histone methyltransferase)

    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].

    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].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 47.8 mg/mL (84.95 mM)

    *"≥" means soluble, but saturation unknown.

    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
    10 mM 0.1777 mL 0.8886 mL 1.7771 mL
    *Please refer to the solubility information to select the appropriate solvent.
    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
    Molecular Weight

    562.71

    Formula

    C₃₀H₄₂N₈O₃

    CAS No.

    1380288-87-8

    SMILES

    NC1=NC=NC2=C1N=CN2[[email protected]]3[[email protected]](O)[[email protected]](O)[[email protected]@H](CN([[email protected]@H]4C[[email protected]](CCC5=NC6=C(C=CC(C(C)(C)C)=C6)N5)C4)C(C)C)O3

    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

    Purity: 99.92%

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    Product Name:
    Pinometostat
    Cat. No.:
    HY-15593
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    Pinometostat

    Cat. No.: HY-15593