EPZ020411 2HCl

製品コードS7820 バッチS782002

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₅H₄₀Cl₂N₄O₃

分子量

515.52

CAS No.

2070015-25-5

Solubility (25°C)*

体外

DMSO

100 mg/mL (193.97 mM)

Water

100 mg/mL (193.97 mM)

Ethanol

100 mg/mL (193.97 mM)

体内（毎回新しく調製した物を用意してください）

	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	5.0mg/ml
	5% DMSO 1 95% Corn oil	0.5mg/ml

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	EPZ020411 is a potent and selective small molecule PRMT6 inhibitor with an IC50 of 10 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].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	A375 cells
	濃度	0-20 μM
	反応時間	48 h
	実験の流れ	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.
動物実験	動物モデル	Sprague-Dawley rats
	投薬量	1 mg/kg
	投与方法	i.v.

参考

[1] Mitchell LH, et al. ACS Med Chem Lett. 2015, 6(6):655-9.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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