Chemical Name: 8-(4-Dibenzothienyl)-2-(4-morpholinyl)-4H-1-benzopyran-4-one
Biological ActivityNU 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%.
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Tocris products are intended for laboratory research use only, unless stated otherwise.
Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing.
Robert et al.
Genome Med., 2015;7:93
Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441.
Zhao et al.
Cancer Res., 2006;66:5354
DNA-dependent protein kinase is a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia.
Willmore et al.
Clin.Cancer Res., 2008;14:3984
Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries.
Leahy et al.
Citations for NU 7441
The citations listed below are publications that use Tocris products. Selected citations for NU 7441 include:
42 Citations: Showing 1 - 10
FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I-induced DNA breakage and transcriptional stress.
Authors: Martínez-Macías Et al.
Life Sci Alliance 2019;2
mEAK-7 Forms an Alternative mTOR Complex with DNA-PKcs in Human Cancer.
Authors: Nguyen Et al.
ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks.
Authors: Balmus Et al.
Nat Commun 2019;10:87
Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation.
Authors: Naumann Et al.
Nat Commun 2018;9:335
The ATM and Rad3-Related (ATR) Protein Kinase Pathway Is Activated by Herpes Simplex Virus 1 and Required for Efficient Viral Replication.
Authors: Edwards Et al.
J Virol 2018;92
In cellulo phosphorylation of DNA double-strand break repair protein XRCC4 on Ser260 by DNA-PK.
Authors: Moghani Et al.
J Radiat Res 2018;59:700
Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders.
Authors: Calo Et al.
DNA Double-Strand Break Resection Occurs during Non-homologous End Joining in G1 but Is Distinct from Resection during Homologous Recombination.
Authors: Biehs Et al.
Mol Cell 2017;65:671
Ionizing radiation response of primary normal human lens epithelial cells.
PLoS One 2017;12:e0181530
DNA-PK triggers histone ubiquitination and signaling in response to DNA double-strand breaks produced during the repair of transcription-blocking topoisomerase I lesions.
Authors: Cristini Et al.
Nucleic Acids Res 2016;44:1161
A novel cytoprotective function for the DNA repair protein Ku in regulating p53 mRNA translation and function.
Authors: Lamaa Et al.
EMBO Rep 2016;17:508
Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways.
Authors: Deng Et al.
PLoS Pathog 2016;12:e1005399
Activation of DNA Damage Response Pathways during Lytic Replication of KSHV.
Authors: Hollingworth Et al.
Nucleic Acids Res 2015;7:2908
Dendritic cells induce Th2-mediated airway inflammatory responses to house dust mite via DNA-dependent protein kinase.
Authors: Mishra Et al.
Mol Cancer Ther 2015;6:6224
NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKcs inhibitor.
Authors: Yu Et al.
Transcriptional elongation requires DNA break-induced signalling.
Authors: Bunch Et al.
Invest Ophthalmol Vis Sci 2015;6:10191
Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.
Authors: Colin Et al.
Pioglitazone restores IGFBP-3 levels through DNA PK in retinal endothelial cells cultured in hyperglycemic conditions.
Authors: Thakran Et al.
Open Biol 2015;56:177
EXO1 is critical for embryogenesis and the DNA damage response in mice with a hypomorphic Nbs1 allele.
Authors: Rein Et al.
Nat Commun 2015;43:7371
Requirement for Parp-1 and DNA ligases 1 or 3 but not of Xrcc1 in chromosomal translocation formation by backup end joining.
Authors: Soni Et al.
Nucleic Acids Res 2014;42:6380
The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair.
Authors: Henriksson Et al.
Genes Dev 2014;28:2726
Identification of synthetic lethality of PRKDC in MYC-dependent human cancers by pooled shRNA screening.
Authors: Zhou Et al.
BMC Cancer 2014;14:944
BRCA2 and RAD51 promote double-strand break formation and cell death in response to gemcit.
Authors: Jones Et al.
J Cell Biol 2014;13:2412
Hypoxic stress facilitates acute activation and chronic downregulation of fanconi anemia proteins.
Authors: Scanlon and Glazer
Mol Cancer Res 2014;12:1016
Human papillomavirus episome stability is reduced by aphidicolin and controlled by DNA damage response pathways.
Authors: Edwards Et al.
J Virol 2013;87:3979
Targeting XRCC1 deficiency in breast cancer for personalized therapy.
Authors: Sultana Et al.
Cancer Res 2013;73:1621
Stathmin regulates mutant p53 stability and transcriptional activity in ovarian cancer.
Authors: Sonego Et al.
EMBO Mol Med 2013;5:707
DNA-PK phosphorylation of IGFBP-3 is required to prevent apoptosis in retinal endothelial cells cultured in high glucose.
Authors: Zhang and Steinle
Neurobiol Dis 2013;54:3052
Senataxin, defective in the neurodegenerative disorder ataxia with oculomotor apraxia 2, lies at the interface of transcription and the DNA damage response.
Authors: Yüce and West
Mol Cell Biol 2013;33:406
Functional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombination.
Authors: Lee Et al.
PLoS One 2013;33:3568
Ataxia telangiectasia mutated (ATM) is dispensable for endonuclease I-SceI-induced homologous recombination in mouse embryonic stem cells.
Authors: Rass Et al.
J Biol Chem 2013;288:7086
DNA-dependent protein kinase regulates DNA end resection in concert with Mre11-Rad50-Nbs1 (MRN) and ataxia telangiectasia-mutated (ATM).
Authors: Zhou and Paull
J Biol Chem 2013;288:37112
A new method for high-resolution imaging of Ku foci to decipher mechanisms of DNA double-strand break repair.
Authors: Britton Et al.
J Cell Biol 2013;202:579
Targeting aberrant DNA double-strand break repair in triple-negative breast cancer with alpha-particle emitter radiolabeled anti-EGFR antibody.
Authors: Song Et al.
Mol Cancer Ther 2013;12:2043
Functional redundancy between the XLF and DNA-PKcs DNA repair factors in V(D)J recombination and nonhomologous DNA end joining.
Authors: Oksenych Et al.
Nat Commun 2013;110:2234
Targeting protein for xenopus kinesin-like protein 2 (TPX2) regulates γ-histone 2AX (γ-H2AX) levels upon ionizing radiation.
Authors: Neumayer Et al.
J Biol Chem 2012;287:42206
Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.
Authors: Yamamoto Et al.
J Virol 2012;198:305
Synthetic lethal targeting of DNA double-strand break repair deficient cells by human apurinic/apyrimidinic endonuclease inhibitors.
Authors: Sultana Et al.
Int J Cancer 2012;131:2433
Parvovirus B19 infection of human primary erythroid progenitor cells triggers ATR-Chk1 signaling, which promotes B19 virus replication.
Authors: Luo Et al.
J Virol 2011;85:8046
Genomic instability, defective spermatogenesis, immunodeficiency, and cancer in a mouse model of the RIDDLE syndrome.
Authors: Bohgaki Et al.
PLoS Genet 2011;7:e1001381
γ-Radiation promotes immunological recognition of cancer cells through increased expression of cancer-testis antigens in vitro and in vivo.
Authors: Sharma Et al.
Invest Ophthalmol Vis Sci 2011;6:e28217
Differential effects of DNA double-strand break repair pathways on single-strand and self-complementary adeno-associated virus vector genomes.
Authors: Cataldi and McCarty
Mol Cell Biol 2010;84:8673
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