Size | Price | Stock | Qty |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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EPZ020411 (EPZ-020411) HCl, the hydrochloride salt of EPZ020411, is a novel and selective inhibitor of PRMT6 (protein arginine methyltransferase, IC50 =10 nM) with therapeutic utility in the treatment of cancer. EPZ020411 shows good bioavailability following subcutaneous dosing in rats making it a suitable tool for in vivo studies.
ln Vitro |
In A375 cells, EPZ020411 hydrochloride (0–20 μM; 24 h) reduces H3R2 methylation[1]. Hair cell survival is increased and neomycin- and cisplatin-induced cell apoptosis is reduced by EPZ020411 hydrochloride (20–40 μM; 6 h)[2].
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ln Vivo |
In C57BL/6J wild-type mice with acute ototoxicity model, EPZ020411 hydrochloride (10 mg/kg; ip once) decreases neomycin- and cisplatin-induced hearing loss[2]. 1.19 Rats' pharmacokinetic parameters for hydrochloride EPZ020411[1]. Rats IV 1 mg/kg Rats SC 5 mg/kg CL (mL/min/kg) 19.7±1.0 Vss (L/kg) 11.1±1.6 t1/2 (h) 8.54±1.43 9.19±1.60 tmax (h) 0.444 Cmax (ng /mL) 844±306 AUC0-τ (h·ng/mL) 745±34 2456±135 AUC0-inf (h·ng/mL) 846±45 2775±181 F (%) 65.6±4.3
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Cell Assay |
Western Blot Analysis[1]
Cell Types: A375 cells Tested Concentrations: 0-20 μM Incubation Duration: 24 hrs (hours) Experimental Results: Dose-dependently diminished H3R2 methylation in A375 cells with an IC50 of 0.634 μM. Cell Viability Assay[2] Cell Types: Cultured cochleae cells Tested Concentrations: 20 and 40 μM Incubation Duration: 6 hrs (hours) Experimental Results: Suppressed the apoptotic cascade induced by aminoglycosides and also inhibited cisplatin-induced apoptosis in the hair cells of the cochlear explants after pretreatment deposed. decreased hair cell loss caused by cisplatin treatment. |
Animal Protocol |
Animal/Disease Models: C57BL/ 6J wild-type mice at P28 with acute ototoxicity model[2]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip)injection; 10 mg/kg once Experimental Results: Dramatically decreased neomycin- and cisplatin-induced HC loss and demonstrated no effect without neomycin injection with mice. |
References |
[1]. Mitchell LH, et al. Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 ToolCompound. ACS Med Chem Lett. 2015 Apr 6;6(6):655-659.
[2]. He Y, et al. Inhibition of Protein arginine methyltransferase 6 reduces reactive oxygen species production and attenuates aminoglycoside- and cisplatin-induced hair cell death. Theranostics. 2020 Jan 1;10(1):133-150. |
Molecular Formula |
C₂₅H₃₉CLN₄O₃
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Molecular Weight |
479.06
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CAS # |
2070015-25-5
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Related CAS # |
EPZ020411;1700663-41-7
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SMILES |
CNCCN(C)CC1=CNN=C1C2=CC=C(O[C@H]3C[C@H](OCCC4CCOCC4)C3)C=C2.Cl[H]
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Synonyms |
EPZ020411 EPZ020411 HCl EPZ-020411 EPZ 020411EPZ020411 hydrochloride
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
0.1 M HCL : 50 mg/mL (~104.37 mM)
DMSO : ~50 mg/mL (~104.37 mM) H2O : ~20 mg/mL (~41.75 mM) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 25 mg/mL (52.19 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0874 mL | 10.4371 mL | 20.8742 mL | |
5 mM | 0.4175 mL | 2.0874 mL | 4.1748 mL | |
10 mM | 0.2087 mL | 1.0437 mL | 2.0874 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.