EPZ020411 2HCl

Catalog No.S7820 Batch:S782001

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Technical Data

Formula

C25H40Cl2N4O3
Molecular Weight 515.52 CAS No. 2070015-25-5
Solubility (25°C)* In vitro DMSO 100 mg/mL (193.97 mM)
Ethanol 100 mg/mL (193.97 mM)
Water 81 mg/mL (157.12 mM)
* <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 EPZ020411 is a potent and selective small molecule PRMT6 inhibitor with an IC50 of 10 nM.
Targets
PRMT6 [1]
(Cell-free assay)		 PRMT1 [1]
(Cell-free assay)		 PRMT8 [1]
(Cell-free assay)
10 nM 119 nM 223 nM
In vitro Treatment with EPZ020411 results in a dose-dependent decrease in H3R2 methylation in A375 human melanoma cells exogenously overexpressing PRMT6(IC50=0.637±0.241 μM). In biochemical assays EPZ020411 is over 100-fold selective for PRMT6/8/1 compared to other histone methyltransferases including four arginine methyltransferases (PRMT3, PRMT4, PRMT5, and PRMT7). The compound shows poor permeability in the parallel artificial membrane permeation assay[1].
In vivo EPZ020411 shows good bioavailability following subcutaneous dosing in rats making it a suitable tool for in vivo studies. Male Sprague-Dawley rats administered a single dose of EPZ020411 at 1 mg/kg by i.v. bolus show a moderate clearance (CL) of 19.7±1.0 mL/min/kg, with a volume of distribution at steady state (Vss) of 11.1±1.6 L/kg, translating to a mean terminal half-life (t1/2) of 8.54±1.43 h. Following 5 mg/kg s.c. dosing, a good bioavailability of 65.6 ± 4.3% is observed, leading to EPZ020411 unbound blood concentration remaining above the PRMT6 biochemical IC50 value for more than 12 h[1].

Protocol (from reference)

Cell Assay:[1]
  • Cell lines

    A375 cells

  • Concentrations

    0-20 μM

  • Incubation Time

    48 h

  • Method

    A375 (CRL-1619) cells are cultured in DMEM plus 10% (vol/vol) FBS. PRMT6 is cloned into BamHI and EcoRI sites of a pcDNA4 HisMAX_A plasmid. Transfection of his-tagged PRMT6 or vector control is carried out using Lipofectamine LTX and Plus reagent according to procedures recommended by the manufacturer. Cells are seeded at 200,000 cells/well in 6-well plates. The following day, the cells are concurrently transfected and treated with compound in 0.25% DMSO. Cells are incubated in the presence of increasing concentrations of compound up to 20 μM. Cell pellets are collected after 48 hours of compound treatment.
Animal Study:[1]
  • Animal Models

    Sprague-Dawley rats

  • Dosages

    1 mg/kg

  • Administration

    i.v.

Selleck's EPZ020411 2HCl has been cited by 3 publications

A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination [ Nat Commun, 2023, 14(1):1430] PubMed: 36932056
Inhibition of PRMT6 reduces neomycin-induced inner ear hair cell injury through the restraint of FoxG1 arginine methylation [ Inflamm Res, 2022, 71(3):309-320] PubMed: 35190853
Inhibition of Protein arginine methyltransferase 6 reduces reactive oxygen species production and attenuates aminoglycoside- and cisplatin-induced hair cell death. [ Theranostics, 2020, 10(1):133-150] PubMed: 31903111

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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.

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