Pinometostat (EPZ5676)

Catalog No.S7062 Batch:S706205

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Technical Data

Formula

C30H42N8O3
Molecular Weight 562.71 CAS No. 1380288-87-8
Solubility (25°C)* In vitro DMSO 100 mg/mL (177.71 mM)
Ethanol 92 mg/mL (163.49 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Pinometostat (EPZ5676) is an S-adenosyl methionine (SAM) competitive inhibitor of protein methyltransferase DOT1L with Ki of 80 pM in a cell-free assay, demonstrating >37,000-fold selectivity against all other PMTs tested, inhibits H3K79 methylation in tumor. Phase 1.
Targets
DOT1L [1]
(Cell-free assay)
80 pM(Ki)
In vitro

EPZ-5676 reduces H3K79 dimethylation with a cellular IC50 of 2.6 nM in MV4-11 cells. EPZ-5676 treatment results in concentration- and time-dependent reduction of H3K79 methylation without effect on the methylation status of other histone sites, which leads to inhibition of key MLL target genes and selective, apoptotic cell killing in MLL-rearranged leukemia cells. EPZ-5676 inhibits proliferation of MLL-AF4 rearranged cell line MV4-11 with an IC50 of 9 nM.
In vivo

EPZ-5676 continuously intravenous infusion for 21 days to xenograft model of MLL-rearranged leukemia, leads to dose-dependent anti-tumor activity. At the highest dose of 70.5 mg/kg/day, complete tumor regressions are achieved with no regrowth for up to 32 days after the cessation of treatment. No significant weight loss or obvious toxicity is observed in rats treated with EPZ-5676 during efficacy study.

Protocol (from reference)

Cell Assay:

[3]
  • Cell lines

    MV4-11 cells

  • Concentrations

    0.003 uM

  • Incubation Time

    4 days

  • Method

    Cells were treated with various concentrations of EPZ-5676.
Animal Study:

[3]
  • Animal Models

    NCr nu/nu mouse

  • Dosages

    20 mg/kg

  • Administration

    i.p.

Customer Product Validation

Data from [Data independently produced by , , Haematologica, 2018, 103(7):1110-1123]

Data from [Data independently produced by , , Theranostics, 2018, 8(16):4359-4371]

Data from [Data independently produced by , , Cell Rep, 2014, 9(3): 1163-70 ]

Data from [Data independently produced by , , Cell Mol Immunol, 2018, doi: 10.1038/s41423-018-0170-4]

Selleck's Pinometostat (EPZ5676) has been cited by 53 publications

Generation of musculoskeletal cells from human urine epithelium-derived presomitic mesoderm cells [ Cell Biosci, 2024, 14(1):93] PubMed: 39010176
Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia [ Int J Mol Sci, 2024, 25(11)6020] PubMed: 38892207
Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells [ Nature, 2023, 620(7974):651-659] PubMed: 37468627
Modelling acquired resistance to DOT1L inhibition exhibits the adaptive potential of KMT2A-rearranged acute lymphoblastic leukemia [ Exp Hematol Oncol, 2023, 12(1):81] PubMed: 37740239
DOT1L activity affects neural stem cell division mode and reduces differentiation and ASNS expression [ EMBO Rep, 2023, e56233.] PubMed: 37382163
H4K20me1 plays a dual role in transcriptional regulation of regeneration and axis patterning in Hydra [ Life Sci Alliance, 2023, 6(5)e202201619] PubMed: 36944423
Modelling acquired resistance to DOT1L inhibition exhibits the adaptive potential of KMT2A-rearranged acute lymphoblastic leukemia [ Exp Hematol Oncol, 2023, 12(1):81] PubMed: 37740239
Retrospective identification of intrinsic factors that mark pluripotency potential in rare somatic cells [ bioRxiv, 2023, 2023.02.10.527870] PubMed: 36798299
Derivation of totipotent-like stem cells with blastocyst-like structure forming potential [ Cell Res, 2022, 10.1038/s41422-022-00668-0] PubMed: 35508506
MOZ and Menin-MLL Complexes are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor [ Cancer Discov, 2022, candisc.0646.2021] PubMed: 35499757

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.