| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
NU7026 is a novel and potent DNA-PK (DNA-dependent protein kinase) with potential antitumor activity. It exhibits a 60-fold higher selectivity for DNA-PK over PI3K, inhibits DNA-PK with an IC50 of 0.23 M in cell-free assays, and has negligible effects on ATM and ATR. NU 7026 is often combined with PARP-1 inhibitor AG14361 to sensitize tumor cells to radio- or chemo-therapy. The NU 7026 treatment (<50 μM) sensitized cells to IR-induced cytotoxicity and decreased clonogenic survival by inhibiting DNA-PK when tested with primary PARP-1-/- and cells PARP-1+/+ cells.
| Targets |
DNA-PK (IC50 = 0.23 μM); PI3K (IC50 = 13 μM)
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| ln Vitro |
NU7026 (10 μM) potentiates ionizing radiation (IR) cytotoxicity [potentiation factor at 90% cell kill (PF90)=1.51±0.04] in exponentially growing DNA-PK proficient but not deficient cells[1]. NU7026 synergistically sensitizes I83 cells to Chlorambucil (CLB) 3.5-fold[2]. NU7026, a brand-new DNA-dependent protein kinase (DNA-PK) inhibitor. A significant radiosensitization effect in CH1 human ovarian cancer cells requires a minimum NU7026 exposure of 4 hours along with 3 Gy of radiation at a dose of 10 M, which is not toxic to cells per se[3].
Solution in vitro: NU7026 is dissolved. Cells are treated with NU7026 at a final DMSO (v/v) concentration of 0.25% DMSO (v/v)[4]. |
| ln Vivo |
NU7026 is a novel DNA-PK（DNA repair enzyme DNA-dependent protein kinase）inhibitor. After being administered intravenously to mice at a dose of 5 mg/kg, NU7026 experienced a quick plasma clearance (0.108 L/h), which is largely attributed to extensive metabolism. Following administration of 20 mg/kg by i.p. or p.o., the bioavailability is 20 and 15%, respectively[3].
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| Enzyme Assay |
Mammalian DNA-PK (500 ng/μL) is isolated from HeLa cell nuclear extract after chromatography using Q-Sepharose, S-Sepharose, and Heparin agarose. In polypropylene 96-well plates, DNA-PK (250 ng) activity is assessed in a buffer containing 25 mM HEPES (pH 7.4), 12.5 mM MgCl2, 50 mM KCl, 1 mM DTT, 10% v/v Glycerol, 0.1% w/v NP-40, and 1 mg of the substrate GST-p53N66 at 30°C in a final volume of 40 μL. Variable NU7026 concentrations are added to the assay mixture (in DMSO at a final concentration of 1% v/v). After 10 minutes of incubation, a 30-mer double-stranded DNA oligonucleotide (final concentration of 0.5 ng/mL) and ATP are added to give a final concentration of 50 μM in order to start the reaction. After 1 hour of shaking, 150 L of PBS are added to the reaction, and 5 μL are then transferred to a 96-well opaque white plate that contains 45 μl of PBS per well. The GSTp53N66 substrate is then given 1 hour to bind to the wells. The sigmoidal plots produced by the graphic package Prism, which plot the enzyme activity against compound concentration in a range of compound concentrations, are used to calculate the IC50s for each compound in each enzyme assay.
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| Cell Assay |
I83 cells are plated in RPMI 1640 medium with 10% FBS (1.5×105 cells/mL) and treated with vehicle (DMSO), 5 μM CLB, CLB IC50, 10 μM NU7026, or the combination of both drugs for 0, 6, 24, and 48 h. Cell cycle distribution, apoptosis, DNA-PK phosphorylation, and γH2AX determination are determined, and they are expressed as a percentage of cells in each phase of the cycle. DNA content is analyzed with a FACSCalibur flow cytometer equipped with CellQuest software[2].
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| Animal Protocol |
Mice[3]
The BALB/c mice used are female. For i.p. and peroral (p.o.) administration, NU7026 is formulated in 10% DMSO and 5% Tween 20 in saline at 20 and 50 mg/kg, respectively. NU7026 is formulated in 10% ethanol, 25% PEG 200, and 5% Tween 20 in saline for i.v. dosing at 5 mg/kg. The vehicle is given to the control animals alone. Per time point, injections are given to groups of three mice. Following halothane's transient anesthesia, blood is taken by cardiac puncture at time points of 0.083, 0.25, 0.5, 1, 2, 4, 6, and 24 hours after administration. Samples are kept at 20°C until analysis after being centrifuged at 1500 g for 2 min to obtain plasma. NU7026 is injected at a rate of 5 mg/kg for studies on urinary excretion. In metabolic cages, urine is collected over a 24-hour period and kept in storage until needed at 20°C. |
| References |
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| Molecular Formula |
C17H15NO3
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|---|---|
| Molecular Weight |
281.3059
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| Exact Mass |
281.10519
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| Elemental Analysis |
C, 72.58; H, 5.37; N, 4.98; O, 17.06
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| CAS # |
154447-35-5
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| Related CAS # |
503465-21-2 (NU-7107); 79105-88-7 (NU-7031); 842122-14-9 (NU-7200); 69541-04-4 (NU-7199)
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| Appearance |
yellow solid powder
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| SMILES |
C1COCCN1C2=CC(=O)C3=C(O2)C4=CC=CC=C4C=C3
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| InChi Key |
KKTZALUTXUZPSN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H15NO3/c19-15-11-16(18-7-9-20-10-8-18)21-17-13-4-2-1-3-12(13)5-6-14(15)17/h1-6,11H,7-10H2
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| Chemical Name |
2-morpholino-4H-benzo[h]chromen-4-one
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| Synonyms |
DNA-PK Inhibitor II; LY-293646; LY 293646; LY293646; NU7026; NU-7026; NU 7026
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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 |
| 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) |
DMSO: ~1 mg/mL (~3.5 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Solubility (In Vivo) |
1% DMSO+30% polyethylene glycol+1% Tween 80: 30mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5548 mL | 17.7740 mL | 35.5480 mL | |
| 5 mM | 0.7110 mL | 3.5548 mL | 7.1096 mL | |
| 10 mM | 0.3555 mL | 1.7774 mL | 3.5548 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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