NU7441 (KU-57788)

NU7441 (KU-57788) is a highly potent and selective DNA-PK inhibitor with IC50 of 14 nM and also inhibits PI3K with IC50 of 5 μM in cell-free assays.

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NU7441 (KU-57788) Chemical Structure

NU7441 (KU-57788) Chemical Structure
Molecular Weight: 413.49

Validation & Quality Control

Customer Product Validation(4)

Quality Control & MSDS

Related Compound Libraries

NU7441 (KU-57788) is available in the following compound libraries:

DNA-PK Inhibitors with Unique Features

  • Non-specific DNA-PK Inhibitor

    PI-103 DNA-PK, IC50=23 nM; p110α/β/δ/γ, IC50=2 nM/3 nM/3 nM/15 nM; mTOR, IC50=30 nM.

  • Most Potent DNA-PK Inhibitor

    PIK-75 DNA-PK, IC50=2 nM.

  • Newest DNA-PK Inhibitor

    KU-0060648 Dual inhibitor of DNA-PK and PI3Kα, PI3Kβ, PI3Kδ with IC50 of 8.6 nM and 4 nM, 0.5 nM, 0.1 nM respectively, less inhibition of PI3Kγ with IC50 of 0.59 μM.

  • Classic DNA-PK Inhibitor

    NU7026 Potent DNA-PK inhibitor with IC50 of 0.23 μM, 60-fold selective for DNA-PK than PI3K and inactive against both ATM and ATR.

Product Information

  • Compare DNA-PK Inhibitors
    Compare DNA-PK Products
  • Research Area
  • Inhibition Profile
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description NU7441 (KU-57788) is a highly potent and selective DNA-PK inhibitor with IC50 of 14 nM and also inhibits PI3K with IC50 of 5 μM in cell-free assays.
Targets DNA-PK [1]
(Cell-free assay)
mTOR [1]
(Cell-free assay)
PI3K [1]
(Cell-free assay)
ATM [1]
(Cell-free assay)
ATR [1]
(Cell-free assay)
IC50 14 nM 1.7 μM 5 μM >100 μM >100 μM
In vitro NU7441 increases the persistence of γH2AX foci after ionizing radiation–induced or etoposide-induced DNA damage. NU7441 (0.5 μM or 1 μM) appreciably increases G2-M accumulation induced by ionizing radiation, etoposide, and doxorubicin in both SW620 and LoVo cells. [2] NU7441 causes persistence of doxorubicin- and ionising radiation-induced DNA double-strand break and also slightly decreases homologous recombination activity DNA-PK-proficient M059-Fus-1 and DNA-PK-deficient M059 J human tumour cells. [3] NU7441 inhibits UV-induced RPA p34 hyperphosphorylation in a dose-dependent manner both in cells lacking and cells expressing polymerase η. [4] NU7441 increases levels of fludarabine-induced γH2AX foci and correspondingly decreased fludarabine-induced cell death in chronic lymphocytic leukemia cells. [5] NU7441 also inhibits mitoxantrone-induced DNA-PKcs autophosphorylation and repair in chronic lymphocytic leukemia cells. [6]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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MV-4-11NF;ZV4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MU\JR|UxRTJwM{ezPUDPxE1?MV\TRW5ITVJ?
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HuH-7NFnEOGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MWXJR|UxRTJwNU[3NFIh|ryPNYq0NWNEW0GQR1XS
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... Click to View More Cell Line Experimental Data

In vivo NU7441 intraperitoneally administrated at dose of 10 mg/kg maintains for at least 4 hours shows nontoxic and increases etoposide-induced tumor growth delay 2-fold in mice bearing SW620 xenografts. [2]
Features

Protocol(Only for Reference)

Cell Assay: [2]

Cell lines SW620, LoVo, V3-YAC and V3 cells
Concentrations 0.5 μM or 1 μM
Incubation Time 17 hours
Method The effect of NU7441 on cellular survival following exposure to etoposide, doxorubicin, and ionizing radiation is measured in SW620, LoVo, V3, and V3-YAC cells by clonogenic assays. Briefly, growing cells in six-well plates or 6-cm dishes are exposed to etoposide or doxorubicin with or without NU7441 (0.5 or 1.0 μM) for 16 hours. For radiosensitization studies, NU7441 is added to the cells 1 hour before irradiation. V3 and V3-YAC cells are exposed to γ-irradiation (3.1 Gy/min 137Cesium). SW620 and LoVo are exposed to X-irradiation (2.9 Gy/min at 230 kV, 10 mA) due to the equipment available. After irradiation, the cells are incubated with or without NU7441 for a further 16 hours. Cells are then harvested by trypsinization, counted, and seeded into 10-cm diameter Petri dishes at densities varying from 100 to 105 per dish in drug-free medium for colony formation. Colonies are stained with crystal violet after 10 to 14 days and counted with an automated colony counter. The survival reduction factor (SRF) is calculated as the surviving fraction of cells in the absence of NU7441 divided by the surviving fraction of cells in the presence of NU7441 for any given dose or concentration of cytotoxic agent. The dose modification ratio (DMR90) is calculated as the concentration/dose of cytotoxic agent required to kill 90% of the cells in the absence of NU7441 divided by the concentration/dose of cytotoxic agent required to kill 90% of the cells in the presence of NU7441.

Animal Study: [2]

Animal Models Female rude mice bearing SW620 xenografts
Formulation Sterile 0.9% sodium chloride solution
Dosages 10 mg/kg
Administration Intraperitoneally administrated

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Leahy JJ, et al. Bioorg Med Chem Lett, 2004, 14(24), 6083-6087.

[2] Zhao Y, et al. Cancer Res, 2006 , 66(10), 5354-5362.

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Chemical Information

Download NU7441 (KU-57788) SDF
Molecular Weight (MW) 413.49
Formula

C25H19NO3S

CAS No. 503468-95-9
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 3 mg/mL (7.25 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 4% DMSO/30% PEG 300/5% Tween 80/ddH2O 1mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 4H-1-Benzopyran-4-one, 8-(4-dibenzothienyl)-2-(4-morpholinyl)-

Customer Product Validation (4)


Click to enlarge
Rating
Source Nucleic Acids Res 2013 41(15), 7378-86. NU7441 (KU-57788) purchased from Selleck
Method EU Immunofluorescence
Cell Lines A2780 ovarian cancer cells
Concentrations 1 uM
Incubation Time 1 h
Results It performed similar experiments using specific inhibitors of DNA-PK. Treatment with Nu7026 or Nu7441 before cisplatin significantly prevented inhibition of rRNA synthesis.

Click to enlarge
Rating
Source Nucleic Acids Res 2013 41, 10157-69. NU7441 (KU-57788) purchased from Selleck
Method Confocal immunostaining
Cell Lines 293T
Concentrations
Incubation Time 30min ,60min
Results the number of IRIFs was reduced significantly in p18CycE-expressing HEK 293T cells compared with parental cells. Pharmacological inhibition of ATM with KU55933 Revealed that S25-53BP1 phosphorylation was ATM-dependent in these cells as IRIFs of S25-53BP1 were abolished in both parental, as well as p18CycE-expressing cells.

Click to enlarge
Rating
Source Toxicol Sci 2014 10.1093/toxsci/kfu207. NU7441 (KU-57788) purchased from Selleck
Method Western blot
Cell Lines H460 cells
Concentrations 1, 3, 10 uM
Incubation Time 1 h
Results It tested 3 concentrations of 2 DNAPK inhibitors (NU7026 and NU7441) for their off-target effects on ATM and ATR signaling in camptothecin-exposed cells. We found that only the highest dose of 60 uM NU7026 clearly diminished ATR activity as evidenced by a lower CHK1 phosphorylation. All doses of both inhibitors eliminated activating autophosphorylation of DNAPK at Ser2056.

Click to enlarge
Rating
Source Dr. Zhang of Tianjin Medical University. NU7441 (KU-57788) purchased from Selleck
Method
Cell Lines A549 cells
Concentrations 0-10 μM
Incubation Time 3 h
Results NU-7441 treatment resulted in a reduction of AKT phosphorylation.

Product Use Citation (14)

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    NU7026 is a potent DNA-PK inhibitor with IC50 of 0.23 μM in cell-free assays, 60-fold selective for DNA-PK than PI3K and inactive against both ATM and ATR.

  • KU-0060648

    KU-0060648 is a dual inhibitor of DNA-PK and PI3Kα, PI3Kβ, PI3Kδ with IC50 of 8.6 nM and 4 nM, 0.5 nM, 0.1 nM respectively, less inhibition of PI3Kγ with IC50 of 0.59 μM.

  • Rapamycin (Sirolimus)

    Rapamycin (Sirolimus) is a specific mTOR inhibitor with IC50 of ~0.1 nM HEK293 cells.

  • MK-2206 2HCl

    MK-2206 2HCl is a highly selective inhibitor of Akt1/2/3 with IC50 of 8 nM/12 nM/65 nM in cell-free assays, respectively; no inhibitory activities against 250 other protein kinases observed. Phase 2.

    Features:The first allosteric small molecule inhibitor of Akt to enter clinical development.

  • CHIR-99021 (CT99021) HCl

    CHIR-99021 (CT99021) HCl is hydrochloride of CHIR-99021, which is a GSK-3α/β inhibitor with IC50 of 10 nM/6.7 nM in cell-free assays; ability to distinguish between GSK-3 and its closest homologs Cdc2 and ERK2.

  • LY294002

    LY294002 is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5 μM/0.57 μM/0.97 μM in cell-free assays, respectively; more stable in solution than Wortmannin, and also blocks autophagosome formation.

  • 3-Methyladenine (3-MA)

    3-Methyladenine (3-MA) is a selective PI3K inhibitor for Vps34 and PI3Kγ with IC50 of 25 μM and 60 μM in HeLa cells; blocks class I PI3K consistently, whereas suppression of class III PI3K is transient, and also blocks autophagosome formation.

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