NU 7026 (Synonyms: DNAPK Inhibitor II, LY293646) |
| Catalog No.GC12332 |
NU 7026 (LY293646) es un nuevo inhibidor especÍfico de DNA-PK con IC50 de 0,23 μM, también inhibe PI3K con IC50 de 13 μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 154447-35-5
Sample solution is provided at 25 µL, 10mM.
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NU 7026 is a selective inhibitor of DNA-PK with IC50 value of 0.23 μM [1].
DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase and involves in a variety of cellular processes, like, DNA double-strand break (DSB) repair, V(D)J recombination apparatus, chromatin structure and telomere maintenance. It has been shown that increased DNA-PK expression resulted in tumor cells resistance to radio- or chemo- therapy [2].
NU 7026 is a potent DNA-PK inhibitor and often is used combined with PARP-1 inhibitor AG14361 to sensitize tumor cells to radio- or chemo-therapy. When tested with primary PARP-1-/- and cells PARP-1+/+ cells, NU 7026 treatment (<50 μM) sensitized cells to IR-induced cytotoxicity and reduced clonogenic survival by inhibiting DNA-PK [1]. In N87 gastric cancer cells, administration NU 7026 combined with radiation increased DNA double-srand break, cell apoptosis and reduced cell survival through inhibiting DNA-PK [2]. When tested with CH1 human ovarian cancer cells, administration of NU 7026 combined with radiation reduced cell survival rate and clonogenic ability [3].
In female BALB/c mice model with CH1 cells subcutaneous xenograft, administration of NU 7026 orally or intraperitoneally sensitized mice to the radiotherapy with the dose of 100 mg/kg [3].
It has also been reported that NU 7026 is a potent inhibitor of PI-3K, ATM and ATR with IC50 value of 13 μM, >100μM and >100μM, respectively [1].
References:
[1]. Veuger, S.J., et al., Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1. Cancer Res, 2003. 63(18): p. 6008-15.
[2]. Niazi, M.T., et al., Effects of dna-dependent protein kinase inhibition by NU7026 on dna repair and cell survival in irradiated gastric cancer cell line N87. Curr Oncol, 2014. 21(2): p. 91-6.
[3]. Nutley, B.P., et al., Preclinical pharmacokinetics and metabolism of a novel prototype DNA-PK inhibitor NU7026. Br J Cancer, 2005. 93(9): p. 1011-8.
| Kinase experiment [1]: | |
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Kinase assays |
DNA-PK activity was measured at 30°C, in a final volume of 40 μl, in 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 in polypropylene 96-well plates. Varying concentrations of inhibitor were added. After 10 min of incubation, ATP was added to give a final concentration of 50 μm, along with a 30-mer double-stranded DNA oligonucleotide to initiate the reaction. After 1 h with shaking, 150 μl of PBS were added to the reaction, and 5 μl were then transferred to a 96-well opaque white plate containing 45 μl of PBS per well, where the GSTp53N66 substrate was allowed to bind to the wells for 1 h. To detect the phosphorylation event on the serine 15 residue of p53 elicited by DNA-PK, a p53 phosphoserine-15 antibody was used in a basic ELISA procedure. |
| Cell experiment [1]: | |
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Cell lines |
CHO cell lines V3 transfected with human DNA-PKcs gene |
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Preparation method |
The solubility of this compound in DMSO is <2.81mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
10 μM |
|
Applications |
NU7026 potentiated ionizing radiation cytotoxicity in exponentially growing DNA-PK proficient cells, which can act as a potent radiosensitizer and shows potential as tools for anticancer therapeutic intervention. |
| Animal experiment [2]: | |
|
Animal models |
Female BALB/c mice |
|
Dosage form |
four times per day at 100 mg/kg, i.p. |
|
Application |
NU7026 shows a significant radiosensitisation effect in BALB/c mice. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Veuger, S.J., et al., Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1. Cancer Res, 2003. 63(18): p. 6008-15. [2] Nutley, B.P., et al., Preclinical pharmacokinetics and metabolism of a novel prototype DNA-PK inhibitor NU7026. Br J Cancer, 2005. 93(9): p. 1011-8. | |
| Cas No. | 154447-35-5 | SDF | |
| Sinónimos | DNAPK Inhibitor II, LY293646 | ||
| Chemical Name | 2-morpholin-4-ylbenzo[h]chromen-4-one | ||
| Canonical SMILES | C1COCCN1C2=CC(=O)C3=C(O2)C4=CC=CC=C4C=C3 | ||
| Formula | C17H15NO3 | M.Wt | 281.31 |
| Solubility | <2.81mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5548 mL | 17.774 mL | 35.548 mL |
| 5 mM | 0.711 mL | 3.5548 mL | 7.1096 mL |
| 10 mM | 0.3555 mL | 1.7774 mL | 3.5548 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 3 reference(s) in Google Scholar.)
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