NU7441 (KU-57788)

Catalog No.S2638 Batch:S263807

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Technical Data

Formula

C25H19NO3S
Molecular Weight 413.49 CAS No. 503468-95-9
Solubility (25°C)* In vitro DMSO 3 mg/mL (7.25 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description NU7441 (KU-57788) is a highly potent and selective DNA-PK inhibitor with IC50 of 14 nM and also inhibits mTOR and PI3K with IC50 of 1.7 μM and 5 μM in cell-free assays, respectively. It reduces the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage.
Targets
DNA-PK [1]
(Cell-free assay)		 mTOR [1]
(cell-free assay)		 PI3K [1]
(cell-free assay)
14 nM 1.7 μM 5 μM
In vitro

NU7441 increases the persistence of γH2AX foci after ionizing radiation–induced DNA damage. NU7441 (0.5 μM or 1 μM) appreciably increases G2-M accumulation induced by ionizing radiation, 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 -induced γH2AX foci and correspondingly decreased -induced cell death in chronic lymphocytic leukemia cells. [5] NU7441 also inhibits -induced DNA-PKcs autophosphorylation and repair in chronic lymphocytic leukemia cells. [6] It reduces the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage[7].
In vivo

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

Protocol (from 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 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 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

  • Dosages

    10 mg/kg

  • Administration

    Intraperitoneally administrated

Customer Product Validation

Data from [Data independently produced by Toxicol Sci, 2014, 10.1093/toxsci/kfu207]

Data from [Data independently produced by Nucleic Acids Res, 2013, 41(15), 7378-86]

Data from [Nucleic Acids Res, 2013, 41, 10157-69]

, , Dr. Zhang of Tianjin Medical University

Selleck's NU7441 (KU-57788) has been cited by 291 publications

Transcription-coupled DNA-protein crosslink repair by CSB and CRL4CSA-mediated degradation [ Nat Cell Biol, 2024, 10.1038/s41556-024-01394-y] PubMed: 38600236
Distinct regulation of ATM signaling by DNA single-strand breaks and APE1 [ Nat Commun, 2024, 15(1):6517] PubMed: 39112456
The Fanconi anemia core complex promotes CtIP-dependent end resection to drive homologous recombination at DNA double-strand breaks [ Nat Commun, 2024, 15(1):7076] PubMed: 39152113
Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089] PubMed: 38453961
DNA-PK inhibition enhances neoantigen diversity and increases T cell responses to immunoresistant tumors [ J Clin Invest, 2024, e180278] PubMed: 39436696
Kaposi's sarcoma herpesvirus exploits the DNA damage response to circularize its genome [ Nucleic Acids Res, 2024, gkad1224] PubMed: 38180827
Switch-like phosphorylation of WRN integrates end-resection with RAD51 metabolism at collapsed replication forks [ Nucleic Acids Res, 2024, gkae807] PubMed: 39315694
The DNA-dependent protein kinase catalytic subunit exacerbates endotoxemia-induced myocardial microvascular injury by disrupting the MOTS-c/JNK pathway and inducing profilin-mediated lamellipodia degradation [ Theranostics, 2024, 14(4):1561-1582] PubMed: 38389837
BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer [ J Exp Clin Cancer Res, 2024, 43(1):163] PubMed: 38863037
DNA-PKcs Phosphorylates Cofilin2 to Induce Endothelial Dysfunction and Microcirculatory Disorder in Endotoxemic Cardiomyopathy [ Research (Wash D C), 2024, 7:0331] PubMed: 38550779

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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