| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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Purity: ≥98%
QNZ (also known as EVP-4593 or CAY-10470), a quinazoline derivative, is a novel and potent NF-κB inhibitor, which shows potent inhibitory activity toward both NF-κB activation and TNF-α production with IC50 of 11 nM and 7 nM in human Jurkat T cells, respectively. It was eliminated using human Jurkat T cells in a luciferase reporter gene-based assay. EVP4593 had neuroprotective effects on GMSLNs in HD and decreased the number of lysosomes/autophagosomes and SOC currents. EVP4593 might be an effective HD medication.
| Targets |
TNF-α (IC50 = 7 nM); NF-κB (IC50 = 11 nM)
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| ln Vitro |
QNZ (Compound 11q) has an anti-inflammatory effect that inhibits the NF-B mediated response. Edema formation is dose-dependently inhibited by QNZ[1]. In Huntington's disease (HD), QNZ (EVP4509) lowers the quantity of lysosomes/autophagosomes and store-operated channel (SOC) currents. It is anticipated that normalizing calcium transport within neurons in response to QNZ will lessen pathology manifestation. Using transmission electron microscopy (TEM), several lysosomes/autophagosomes are examined in HD and WT neurons treated with QNZ. While WT neurons are unaffected, incubation with QNZ almost doubles the amount of lysosomes/autophagosomes in HD GABAergic Medium Spiny (GABA MS)-like Neurons (GMSLNs) (from 0.41±0.04 to 0.23±0.04; p<0.05). By using flow cytometry (FC) analysis to look at lysosome content, this observation is confirmed. In HD GMSLNs, the median fluorescence intensity decreases by 34±6 percent after QNZ treatment (p<0.05)[2].
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| ln Vivo |
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| Enzyme Assay |
In RPMI1640 with 10% FCS, human Jurkat T cells are cultured at 37 °C in a 5% CO2 environment. The cells are transiently transfected with 1 μg of pNFκB-Luc using the SuperFect Transfection Reagent after being plated in 6-well plates (2×106/well). The cells undergo overnight culture at 37°C following transfection. Then, they are collected, resuspended in new medium, and plated in 96-well plates (2×105/well). The cells are placed in 96-well plates, and EVP4593 is dissolved in DMSO and added at the proper concentrations. The plates are then incubated at 37°C for an hour. For the purpose of triggering transcription, 10 ng/mL of PMA and 100 μg/mL of PHA are added to each well, and the cells are then incubated for an additional 6 hours at 37°C. Cell lysis buffer containing luciferase substrate is added to each well after the culture media have been removed. The luminescence is then immediately measured with a Packard Topcount after each portion has been transferred to a black 96-well plate. A nonlinear regression technique is used to determine the 50% inhibitory concentration (IC50) values.
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| Cell Assay |
iPSHD22 cells are cultured in K-4 medium in a 96-well black plates with clear flat bottom. Before being analyzed, cells are then exposed to chemicals for 24 hours (for example, QNZ 100 nM). Luminescent assay To simultaneously count the proportion of alive (viability) and dead (cytotoxicity) cells in each well, the MultiTox-Fluor Multiplex Cytotoxicity Assay is used. DTX 880 Multimode Microplate Reader is used to find fluorescence. Using the equation ([cytotoxicity in a well with cells]-([cytotoxicity in a well without cells])/([viability in a well with cells]-([viability in a well without cells])[2], the level of cell death (LoCD) is assessed.
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| Animal Protocol |
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| References |
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| Molecular Formula |
C22H20N4O
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| Molecular Weight |
356.42
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| Exact Mass |
356.16
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| Elemental Analysis |
C, 74.14; H, 5.66; N, 15.72; O, 4.49
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| CAS # |
545380-34-5
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| Appearance |
Solid powder
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| SMILES |
C1=CC=C(C=C1)OC2=CC=C(C=C2)CCNC3=NC=NC4=C3C=C(C=C4)N
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| InChi Key |
IBAKVEUZKHOWNG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H20N4O/c23-17-8-11-21-20(14-17)22(26-15-25-21)24-13-12-16-6-9-19(10-7-16)27-18-4-2-1-3-5-18/h1-11,14-15H,12-13,23H2,(H,24,25,26)
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| Chemical Name |
4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine
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| Synonyms |
CAY10470; CAY 10470; CAY-10470; EVP 4593; EVP-4593; EVP4593; QNZ
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.01 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 (7.01 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 (7.01 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: 0.5% hydroxyethyl cellulose: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8057 mL | 14.0284 mL | 28.0568 mL | |
| 5 mM | 0.5611 mL | 2.8057 mL | 5.6114 mL | |
| 10 mM | 0.2806 mL | 1.4028 mL | 2.8057 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.
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