NU 7441

Cat. No. 3712

NU 7441 C25H19NO3S [503468-95-9]

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Alternative Name: KU 57788

Chemical Name: 8-(4-Dibenzothienyl)-2-(4-morpholinyl)-4H-1-benzopyran-4-one

Biological Activity

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

Soluble to 5 mM in DMSO with gentle warming
>99 %
Store at +4°C

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
All Tocris products are intended for laboratory research use only.

Certificate of Analysis / Safety Data Sheet

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Robert et al (2015) Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing. Genome Med. 7 93. PMID: 26307031.

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.

Zhao et al (2006) Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res. 66 5354. PMID: 16707462.

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.

If you know of a relevant reference for this product please let us know.

Citations are publications that use Tocris products. Selected citations for NU 7441 include:

Bunch et al (2015) Transcriptional elongation requires DNA break-induced signalling. Invest Ophthalmol Vis Sci 6 10191. PMID: 26671524.

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.

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.

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.

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.

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.

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.

Jones et al (2014) BRCA2 and RAD51 promote double-strand break formation and cell death in response to gemcitabine. J Cell Biol 13 2412. PMID: 25053826.

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.

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.

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.

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.

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.

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.

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.

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.

Yamamoto et al (2012) Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice. J Virol 198 305. PMID: 22869596.

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.

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.

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.

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Keywords: NU 7441, supplier, potent, selective, DNA-dependent, protein, kinases, inhibitors, inhibits, Checkpoint, Control, Kinases, DNA-PK, NU7441, KU57788, CRISPR, Cas9, HDR, NHEJ, homology, directed, repair, nonhomologous, end, joining, Tocris Bioscience, DNA-Dependent Protein Kinase Inhibitor products

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