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Submit ReviewNU 7441
Description: Potent and selective DNA-PK inhibitor
Alternative Names: KU 57788
Chemical Name: 8-(4-Dibenzothienyl)-2-(4-morpholinyl)-4H-1-benzopyran-4-one
Purity: ≥99% (HPLC)
Biological Activity for NU 7441
NU 7441 is a potent and selective DNA-PK inhibitor (IC50 = 14 nM). Selective for DNA-PK over a range of kinases including mTOR, PI 3-K, ATM and ATR. Potentiates the effects of doxorubicin (Cat. No. 2252) and etoposide (Cat. No. 1226) in vitro and etoposide in vivo. Also enhances CRISPR-Cas9-mediated homology-directed repair (HDR) efficiency 2 to 3-fold, and decreases nonhomologous end-joining (NHEJ) frequency ~40%.
Technical Data for NU 7441
| M. Wt | 413.49 |
| Formula | C25H19NO3S |
| Storage | Store at +4°C |
| Purity | ≥99% (HPLC) |
| CAS Number | 503468-95-9 |
| PubChem ID | 11327430 |
| InChI Key | JAMULYFATHSZJM-UHFFFAOYSA-N |
| Smiles | O=C1C3=C(C(C4=CC=CC5=C4SC6=C5C=CC=C6)=CC=C3)OC(N2CCOCC2)=C1 |
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
Solubility Data for NU 7441
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 2.07 | 5 with gentle warming |
Preparing Stock Solutions for NU 7441
The following data is based on the product molecular weight 413.49. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 0.05 mM | 48.37 mL | 241.84 mL | 483.69 mL |
| 0.25 mM | 9.67 mL | 48.37 mL | 96.74 mL |
| 0.5 mM | 4.84 mL | 24.18 mL | 48.37 mL |
| 2.5 mM | 0.97 mL | 4.84 mL | 9.67 mL |
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Product Datasheets for NU 7441
References for NU 7441
References are publications that support the biological activity of the product.
Zhao et al (2006) Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res. 66 5354 PMID: 16707462
Willmore et al (2008) DNA-dependent protein kinase is a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia. Clin.Cancer Res. 14 3984 PMID: 18559621
Leahy et al (2004) Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorg.Med.Chem.Lett. 14 6083 PMID: 15546735
Robert et al (2015) Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing. Genome Med. 7 93 PMID: 26307031
If you know of a relevant reference for NU 7441, please let us know.
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54 Citations for NU 7441
Citations are publications that use Tocris products. Selected citations for NU 7441 include:
Nguyen et al (2019) mEAK-7 Forms an Alternative mTOR Complex with DNA-PKcs in Human Cancer. iScience 17 190 PMID: 31288154
Yu et al (2015) NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKcs inhibitor. Oncotarget 6 3848 PMID: 25714019
Zhang and Steinle (2013) DNA-PK phosphorylation of IGFBP-3 is required to prevent apoptosis in retinal endothelial cells cultured in high glucose. Neurobiol Dis 54 3052 PMID: 23557743
Sonego et al (2013) Stathmin regulates mutant p53 stability and transcriptional activity in ovarian cancer. EMBO Mol Med 5 707 PMID: 23610071
Sultana et al (2012) Synthetic lethal targeting of DNA double-strand break repair deficient cells by human apurinic/apyrimidinic endonuclease inhibitors. Int J Cancer 131 2433 PMID: 22377908
B Matija et al (2012) Unmodified histone H3K4 and DNA-dependent protein kinase recruit autoimmune regulator to target genes. Mol Cell Biol 32 1354-62 PMID: 22310661
Martínez-Macías et al (2019) FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I-induced DNA breakage and transcriptional stress. Life Sci Alliance 2 PMID: 30808650
Dale A et al (2017) Regulation of human polλ by ATM-mediated phosphorylation during non-homologous end joining. DNA Repair (Amst) 51 31-45 PMID: 28109743
Biehs et al (2017) DNA Double-Strand Break Resection Occurs during Non-homologous End Joining in G1 but Is Distinct from Resection during Homologous Recombination. Mol Cell 65 671 PMID: 28132842
Lamaa et al (2016) A novel cytoprotective function for the DNA repair protein Ku in regulating p53 mRNA translation and function. EMBO Rep 17 508 PMID: 26964895
Cristini et al (2016) DNA-PK triggers histone ubiquitination and signaling in response to DNA double-strand breaks produced during the repair of transcription-blocking topoisomerase I lesions. Nucleic Acids Res 44 1161 PMID: 26578593
Sultana et al (2013) Targeting XRCC1 deficiency in breast cancer for personalized therapy. Cancer Res 73 1621 PMID: 23253910
Neumayer et al (2012) Targeting protein for xenopus kinesin-like protein 2 (TPX2) regulates γ-histone 2AX (γ-H2AX) levels upon ionizing radiation. J Biol Chem 287 42206 PMID: 23045526
Cataldi and McCarty (2010) Differential effects of DNA double-strand break repair pathways on single-strand and self-complementary adeno-associated virus vector genomes. Mol Cell Biol 84 8673 PMID: 20538857
Lora A et al (2019) TOP2β-Dependent Nuclear DNA Damage Shapes Extracellular Growth Factor Responses via Dynamic AKT Phosphorylation to Control Virus Latency. Mol Cell 74 466-480.e4 PMID: 30930055
Calo et al (2018) Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders. Nature 554 112 PMID: 29364875
Scanlon and Glazer (2014) Hypoxic stress facilitates acute activation and chronic downregulation of fanconi anemia proteins. Mol Cancer Res 12 1016 PMID: 24688021
Ronald et al (2013) Repair of DNA strand breaks in a minichromosome in vivo: kinetics, modeling, and effects of inhibitors. PLoS One 8 e52966 PMID: 23382828
Naumann et al (2018) Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation. Nat Commun 9 335 PMID: 29362359
Deng et al (2016) Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways. PLoS Pathog 12 e1005399 PMID: 26765330
Yamamoto et al (2012) Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice. J Virol 198 305 PMID: 22869596
Soni et al (2014) Requirement for Parp-1 and DNA ligases 1 or 3 but not of Xrcc1 in chromosomal translocation formation by backup end joining. Nucleic Acids Res 42 6380 PMID: 24748665
Bohgaki et al (2011) Genomic instability, defective spermatogenesis, immunodeficiency, and cancer in a mouse model of the RIDDLE syndrome. PLoS Genet 7 e1001381 PMID: 21552324
Joseph R et al (2023) Ku-DNA binding inhibitors modulate the DNA damage response in response to DNA double-strand breaks. NAR Cancer 5 zcad003 PMID: 36755959
Min Sup et al (2023) DNA damage repair kinase DNA-PK and cGAS synergize to induce cancer-related inflammation in glioblastoma. EMBO J 42 e111961 PMID: 36574362
Keith W et al (2020) Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair. Nucleic Acids Res 48 6672-6684 PMID: 32504494
S-D et al (2020) Oxidative DNA damage is concurrently repaired by base excision repair (BER) and apyrimidinic endonuclease 1 (APE1)-initiated nonhomologous end joining (NHEJ) in cortical neurons. Neuropathol Appl Neurobiol 46 375-390 PMID: 31628877
Markus et al (2020) Combining PARP and DNA-PK Inhibitors With Irradiation Inhibits HPV-Negative Head and Neck Cancer Squamous Carcinoma Growth. Front Genet 11 1036 PMID: 33133138
Jessica M et al (2020) Oocytes can efficiently repair DNA double-strand breaks to restore genetic integrity and protect offspring health. Proc Natl Acad Sci U S A 117 11513-11522 PMID: 32381741
Thomas L et al (2020) Synergistic gene editing in human iPS cells via cell cycle and DNA repair modulation. Nat Commun 11 2876 PMID: 32513994
Edwards et al (2018) The ATM and Rad3-Related (ATR) Protein Kinase Pathway Is Activated by Herpes Simplex Virus 1 and Required for Efficient Viral Replication. J Virol 92 PMID: 29263259
Moghani et al (2018) In cellulo phosphorylation of DNA double-strand break repair protein XRCC4 on Ser260 by DNA-PK. J Radiat Res 59 700 PMID: 30247612
Hamada (2017) Ionizing radiation response of primary normal human lens epithelial cells. PLoS One 12 e0181530 PMID: 28746371
Bunch et al (2015) Transcriptional elongation requires DNA break-induced signalling. Invest Ophthalmol Vis Sci 6 10191 PMID: 26671524
Thakran et al (2015) Pioglitazone restores IGFBP-3 levels through DNA PK in retinal endothelial cells cultured in hyperglycemic conditions. Open Biol 56 177 PMID: 25525174
Colin et al (2015) Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins. Viruses 5 140156 PMID: 25761368
Hollingworth et al (2015) Activation of DNA Damage Response Pathways during Lytic Replication of KSHV. Nucleic Acids Res 7 2908 PMID: 26057167
Rein et al (2015) EXO1 is critical for embryogenesis and the DNA damage response in mice with a hypomorphic Nbs1 allele. Nat Commun 43 7371 PMID: 26160886
Mishra et al (2015) Dendritic cells induce Th2-mediated airway inflammatory responses to house dust mite via DNA-dependent protein kinase. Mol Cancer Ther 6 6224 PMID: 25692509
Zhou and Paull (2013) DNA-dependent protein kinase regulates DNA end resection in concert with Mre11-Rad50-Nbs1 (MRN) and ataxia telangiectasia-mutated (ATM). J Biol Chem 288 37112 PMID: 24220101
Yüce and West (2013) Senataxin, defective in the neurodegenerative disorder ataxia with oculomotor apraxia 2, lies at the interface of transcription and the DNA damage response. Mol Cell Biol 33 406 PMID: 23149945
Edwards et al (2013) Human papillomavirus episome stability is reduced by aphidicolin and controlled by DNA damage response pathways. J Virol 87 3979 PMID: 23365423
Rass et al (2013) Ataxia telangiectasia mutated (ATM) is dispensable for endonuclease I-SceI-induced homologous recombination in mouse embryonic stem cells. J Biol Chem 288 7086 PMID: 23355489
Song et al (2013) Targeting aberrant DNA double-strand break repair in triple-negative breast cancer with alpha-particle emitter radiolabeled anti-EGFR antibody. Mol Cancer Ther 12 2043 PMID: 23873849
Britton et al (2013) A new method for high-resolution imaging of Ku foci to decipher mechanisms of DNA double-strand break repair. J Cell Biol 202 579 PMID: 23897892
Sharma et al (2011) γ-Radiation promotes immunological recognition of cancer cells through increased expression of cancer-testis antigens in vitro and in vivo. Invest Ophthalmol Vis Sci 6 e28217 PMID: 22140550
Balmus et al (2019) ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks. Nat Commun 10 87 PMID: 30622252
Jones et al (2014) BRCA2 and RAD51 promote double-strand break formation and cell death in response to gemcit. J Cell Biol 13 2412 PMID: 25053826
Lee et al (2013) Functional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombination. PLoS One 33 3568 PMID: 23836881
Oksenych et al (2013) Functional redundancy between the XLF and DNA-PKcs DNA repair factors in V(D)J recombination and nonhomologous DNA end joining. Nat Commun 110 2234 PMID: 23345432
Luo et al (2011) Parvovirus B19 infection of human primary erythroid progenitor cells triggers ATR-Chk1 signaling, which promotes B19 virus replication. J Virol 85 8046 PMID: 21680529
Lei et al (2021) Dynamics and competition of CRISPR-Cas9 ribonucleoproteins and AAV donor-mediated NHEJ, MMEJ and HDR editing. Nucleic Acids Res 49 969-985 PMID: 33398341
Henriksson et al (2014) The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair. Genes Dev 28 2726 PMID: 25512560
Zhou et al (2014) Identification of synthetic lethality of PRKDC in MYC-dependent human cancers by pooled shRNA screening. BMC Cancer 14 944 PMID: 25495526
Do you know of a great paper that uses NU 7441 from Tocris? Please let us know.
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Inhibition of NU 7441 results in DNA damage.
By
Anonymous on 02/29/2020
Assay Type: In Vitro
Species: Human
Cell Line/Tissue: hela
HeLa cells transfected with in vitro transcribed I-PpoI and treated or not with inhibitors for KU 55933 and NU 7441 (iDPK)
Literature in this Area
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Cell Cycle and DNA Damage Research Product Guide
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In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. This poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.