NU7441 (KU57788)

Alias: NU7441; NU 7441; NU-7441; KU 57788; KU57788; KU-57788
Cat No.:V0108 Purity: ≥98%
NU7441 (also called KU-57788) is a highly potent, selective and ATP-competitive inhibitor of DNA-PK (DNA-dependent protein kinase) with IC50 of 14 nM, has anticancer activity.
NU7441 (KU57788) Chemical Structure CAS No.: 503468-95-9
Product category: PI3K
This product is for research use only, not for human use. We do not sell to patients.
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10mg
25mg
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

NU7441 (also called KU-57788) is a highly potent, selective and ATP-competitive inhibitor of DNA-PK (DNA-dependent protein kinase) with IC50 of 14 nM, has anticancer activity. Additionally, it inhibits PI3K in cell-free assays with an IC50 value of 5 M. At a concentration of 100 μM, the DNA-PK-related enzymes ATM and ATR were not inhibited by NU7441. With IC50 values for mTOR and PI3K that were 1.7 and 5 M, respectively—roughly 100 times higher than the IC50 value for DNA-PK—NU7441 demonstrated inhibition activities. In vitro, NU7441 made HeLa cells more sensitive to ionizing radiation, with dose modification factors of 2.5 at 10% survival being seen at 0.5 microM.

Biological Activity I Assay Protocols (From Reference)
Targets
DNA-PK (IC50 = 14 nM); mTOR (IC50 = 1.7 μM); PI3K (IC50 = 5.0 μM); CRISPR/Cas9
ln Vitro
NU7441 increases the persistence of γH2AX foci after ionizing radiation–induced or etoposide-induced DNA damage. In both SW620 and LoVo cells, NU7441 (0.5 μM or 1 μM) significantly increases G2-M accumulation brought on by ionizing radiation, etoposide, and doxorubicin. [2] In addition to making DNA double-strand breaks more persistent, NU7441 also slightly reduces the activity of homologous recombination in DNA-PK-sufficient M059-Fus-1 and DNA-PK-sufficient M059 J human tumor cells.[3] In cells that express polymerase as well as those that lack it, NU7441 inhibits UV-induced RPA p34 hyperphosphorylation in a dose-dependent manner. [4] In chronic lymphocytic leukemia cells, NU7441 causes fludarabine-induced H2AX foci to accumulate and, in turn, reduces fludarabine-induced cell death. [5] In addition, DNA-PKcs autophosphorylation and repair brought on by mitoxantrone in cells of chronic lymphocytic leukemia are inhibited by NU7441.[6] In the aftermath of Cas9-mediated DNA cleavage, it decreases the frequency of NHEJ while increasing the rate of HDR[7].
ln vivo
In mice bearing SW620 xenografts, administration of NU7441 intraperitoneally at a dose of 10 mg/kg for at least 4 hours demonstrates nontoxicity and increases etoposide-induced tumor growth delay by a factor of two.[2]
Enzyme Assay
NU7441 (also called KU-57788) is a highly potent, selective and ATP-competitive DNA-PK inhibitor with IC50 of 14 nM. It also inhibits PI3K with IC50 value of 5 μM in cell-free assays.
Cell Assay
HepG2 cells (4000 per well) are cultured in a 96-well plate for 24 h. The culture media are then supplemented with concentrations of 0.1 µM, 1 µM, 5 µM, and 10 µM of KU-57788 once the cells have finished adhering. 10% CCK-8 solution is added to the culture media after KU-57788 treatment has been going on for 12 hours.Incubation is then continued for another 2 hours. A spectrometer is used to calculate the OD450 values, and the results are then analyzed to calculate the rate of cell growth.
Animal Protocol
Female rude mice bearing SW620 xenografts
10 mg/kg
Intraperitoneally administrated
References

[1]. Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6083-7.

[2]. NU7441 Enhances the Radiosensitivity of Liver Cancer Cells. Cell Physiol Biochem. 2016;38(5):1897-905.

[3]. Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach. J Med Chem. 2005 Dec 1;48(24):7829-46.

[4]. The acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors. ACS Chem Biol. 2014 Feb 25.

[5]. Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing. Genome Med. 2015 Aug 27;7:93.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C25H19NO3S
Molecular Weight
413.49
Exact Mass
413.10856
Elemental Analysis
C, 72.62; H, 4.63; N, 3.39; O, 11.61; S, 7.75
CAS #
503468-95-9
Appearance
Off-white to beige solid powder
SMILES
C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC5=C4SC6=CC=CC=C56
InChi Key
JAMULYFATHSZJM-UHFFFAOYSA-N
InChi Code
InChI=1S/C25H19NO3S/c27-21-15-23(26-11-13-28-14-12-26)29-24-17(6-3-9-20(21)24)19-8-4-7-18-16-5-1-2-10-22(16)30-25(18)19/h1-10,15H,11-14H2
Chemical Name
8-dibenzothiophen-4-yl-2-morpholin-4-ylchromen-4-one
Synonyms
NU7441; NU 7441; NU-7441; KU 57788; KU57788; KU-57788
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO: ~4 mg/mL warming (~9.7 mM)
Water: <1 mg/mL (slightly soluble or insoluble)
Ethanol: <1 mg/mL (slightly soluble or insoluble)
Solubility (In Vivo)
4%DMSO+30%PEG 300+5%Tween 80+ddH2O: 1.0mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.4184 mL 12.0922 mL 24.1844 mL
5 mM 0.4837 mL 2.4184 mL 4.8369 mL
10 mM 0.2418 mL 1.2092 mL 2.4184 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.

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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.
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Biological Data
  • NU7441 (KU-57788)

    NU7441 (0.3 μM) enhances cellular senescence in irradiated H1299 cells.2016 Sep;107(9):1250-5.

  • NU7441 (KU-57788)

    Both X‐rays and carbon ions induce radio‐sensitization in non‐small cell lung cancer (NSCLC) cells with nontoxic conce ntrations of NU7441 treatment.2016 Sep;107(9):1250-5.

  • NU7441 (KU-57788)

    Non‐small cell lung cancer (NSCLC) cells treated with NU7441 (0.3 μM) and radiation show significant G2/M arrest.2016 Sep;107(9):1250-5.

  • NU7441 (KU-57788)

    Low concentration of NU7441 does not seem to show double strand break (DSB) repair inhibition in X‐ray‐irradiated and carbon‐irradiated non‐small cell lung cancer (NSCLC) cells.2016 Sep;107(9):1250-5.

  • NU7441 (KU-57788)

    NU7441 (0.3 μM) causes a remarkable increase of DNA fragmentation in irradiated H1299 cells.2016 Sep;107(9):1250-5.

  • NU7441 (KU-57788)

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