Chemical Name: 2-(4-Morpholinyl)-6-(1-thianthrenyl)-4H-pyran-4-one
Biological ActivityKU 55933 is a potent, selective and competitive ATM kinase inhibitor (Ki = 2.2 nM, IC50 values are 13, 2500, 9300, 16600, > 100000 and > 100000 nM at ATM, DNA-PK, mTOR, PI 3-kinase, PI 4-K and ATR respectively). Decreases viability of MCF-7, A549 and HCT116 cells and decreases p21CIP1 levels in vitro. Acts as a radio- and chemosensitizer for the treatment of cancer.
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Tocris products are intended for laboratory research use only, unless stated otherwise.
Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM.
Hickson I, Zhao Y, Richardson CJ et al.
Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced senescent tumor cells: Implications for chemotherapy.
Crescenzi et al.
Clin.Cancer Res., 2008;14:1877
Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis.
Eaton et al.
Citations for KU 55933
The citations listed below are publications that use Tocris products. Selected citations for KU 55933 include:
77 Citations: Showing 1 - 10
Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response.
Authors: Rosina Et al.
Sci Rep 2019;9:5447
Protein Phosphatase 1 Regulatory Subunit SDS22 Inhibits Breast Cancer Cell Tumorigenesis by Functioning as a Negative Regulator of the AKT Signaling Pathway.
Authors: Paul Et al.
Cytotoxic and Antitumor Activity of Lactaptin in Combination with Autophagy Inducers and Inhibitors.
Authors: Bagamanshina Et al.
Biomed Res Int 2019;2019:4087160
Autophagy is required for lung development and morphogenesis.
Authors: Yeganeh Et al.
J Clin Invest 2019;130:2904
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
Typhoid toxin exhausts the RPA response to DNA replication stress driving senescence and Salmonella infection.
Authors: Ibler Et al.
Nat Commun 2019;10:4040
The CHD6 chromatin remodeler is an oxidative DNA damage response factor.
Authors: Moore Et al.
Nat Commun 2019;10:241
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
Formation of 53BP1 foci and ATM activation under oxidative stress is facilitated by RNA:DNA hybrids and loss of ATM-53BP1 expression promotes photoreceptor cell survival in mice.
Authors: Bhatia Et al.
The Histone Chaperone FACT Coordinates H2A.X-Dependent Signaling and Repair of DNA Damage.
Authors: Piquet Et al.
Mol Cell 2018;72:888
The Chromatin Reader ZMYND8 Regulates Igh Enhancers to Promote Immunoglobulin Class Switch Recombination.
Authors: Delgado-Benito Et al.
Mol Cell 2018;72:636
Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders.
Authors: Calo Et al.
Cell type-dependent bimodal p53 activation engenders a dynamic mechanism of chemoresistance.
Authors: Yang Et al.
Sci Adv 2018;4:eaat5077
SETD2-dependent H3K36me3 plays a critical role in epigenetic regulation of the HPV31 life cycle.
Authors: Gautam Et al.
PLoS Pathog 2018;14:e1007367
Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy.
Authors: Benkafadar Et al.
EMBO Mol Med 2017;9:7
ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration.
Authors: Jaiswal Et al.
EMBO J 2017;36:2161
NOX2-dependent ATM kinase activation dictates pro-inflammatory macrophage phenotype and improves effectiveness to radiation therapy.
Authors: Wu Et al.
Cell Death Differ 2017;24:1632
Drug-induced hyperploidy stimulates an antitumor NK cell response mediated by NKG2D and DNAM-1 receptors.
Authors: Acebes-Huerta Et al.
A USP28-53BP1-p53-p21 signaling axis arrests growth after centrosome loss or prolonged mitosis.
Authors: Lambrus Et al.
J Cell Biol 2016;214:143
Fe65 Is Phosphorylated on Ser289 after UV-Induced DNA Damage.
Authors: Langlands Et al.
PLoS One 2016;11:e0155056
Activation of DNA Damage Response Pathways during Lytic Replication of KSHV.
Authors: Hollingworth Et al.
Mol Cell Biol 2015;7:2908
Selective Inhibition of Parallel DNA Damage Response Pathways Optimizes Radiosensitization of Glioblastoma Stem-like Cells.
Authors: Ahmed Et al.
Cancer Res 2015;75:4416
A radiosensitivity MiRNA signature validated by the TCGA database for head and neck squamous cell carcinomas.
Authors: Liu Et al.
Aging Cell 2015;6:34649
DNA Damage Response Proteins and Oxygen Modulate Prostaglandin E2 Growth Factor Release in Response to Low and High LET Ionizing Radiation.
Authors: Allen Et al.
Front Oncol 2015;5:260
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.
The E3 ubiquitin ligase ARIH1 protects against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest.
Authors: Stechow Et al.
Proc Natl Acad Sci U S A 2015;35:1254
Trovafloxacin-induced replication stress sensitizes HepG2 cells to tumor necrosis factor-alpha-induced cytotoxicity mediated by extracellular signal-regulated kinase and ataxia telangiectasia and Rad3-related.
Authors: Beggs Et al.
Spatio-temporal regulation of RAG2 following genotoxic stress.
Authors: Rodgers Et al.
DNA Repair (Amst) 2015;27:19
Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage.
Authors: Gibbs-Seymour Et al.
Open Biol 2015;14:162
Pharmacologic inhibition of ATR and ATM offers clinically important distinctions to enhancing platinum or radiation response in ovarian, endometrial, and cervical cancer cells.
Authors: Teng Et al.
Gynecol Oncol 2015;136:554
F-box protein FBXO31 directs degradation of MDM2 to facilitate p53-mediated growth arrest following genotoxic stress.
Authors: Malonia Et al.
J Cell Biol 2015;112:8632
Contrasting Effects of the Cytotoxic Anticancer Drug gemcit. and the EGFR Tyrosine Kinase Inhibitor gefi. on NK Cell-Mediated Cytotoxicity via Regulation of NKG2D Ligand in Non-Small-Cell Lung Cancer Cells.
Authors: Okita Et al.
PLoS One 2015;10:e0139809
TLR8 signaling enhances tumor immunity by preventing tumor-induced T-cell senescence.
Authors: Ye Et al.
EMBO Mol Med 2014;6:1294
SMAR1 coordinates HDAC6-induced deacetylation of Ku70 and dictates cell fate upon irradiation.
Authors: Chaudhary Et al.
Cell Death Dis 2014;5:e1447
ATM specifically mediates repair of double-strand breaks with blocked DNA ends.
Authors: Alvarez-Quilón Et al.
Nat Commun 2014;5:3347
Inhibition of ataxia telangiectasia mutated (ATM) kinase suppresses herpes simplex virus type 1 (HSV-1) keratitis.
Authors: Alekseev Et al.
Invest Ophthalmol Vis Sci 2014;55:706
Defying DNA double-strand break-induced death during prophase I meiosis by temporal TAp63α phosphorylation regulation in developing mouse oocytes.
Authors: Kim and Suh
Mol Cell Biol 2014;34:1460
The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair.
Authors: Henriksson Et al.
Genes Dev 2014;28:2726
Selenoprotein H suppresses cellular senescence through genome maintenance and redox regulation.
Authors: Wu Et al.
J Biol Chem 2014;289:34378
Preconditioning stimuli induce autophagy via sphingosine kinase 2 in mouse cortical neurons.
Authors: Sheng Et al.
Wild-type p53-induced phosphatase 1 (Wip1) forestalls cellular premature senescence at physiological oxygen levels by regulating DNA damage response signaling during DNA replication.
Authors: Sakai Et al.
Cell Cycle 2014;13:1015
SMC1-mediated intra-S-phase arrest facilitates bocavirus DNA replication.
Authors: Luo Et al.
J Virol 2013;87:4017
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
ATP-competitive mTOR kinase inhibitors delay plant growth by triggering early differentiation of meristematic cells but no developmental patterning change.
Authors: Montané and Menand
Nat Chem Biol 2013;64:4361
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
Mechanism of DNA resection during intrachromosomal recombination and immunoglobulin class switching.
Authors: Bothmer Et al.
Hairpin-end conformation of adeno-associated virus genome determines interactions with DNA-repair pathways.
Authors: Cataldi and McCarty
J Biol Chem 2013;20:686
Ionizing radiation enhances dl922-947-mediated cell death of anaplastic thyroid carcinoma cells.
Authors: Passaro Et al.
Endocr Relat Cancer 2013;20:633
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
E1a promotes c-Myc-dependent replicative stress: implications in glioblastoma radiosensitization.
Authors: Valero Et al.
Cell Cycle 2013;13:52
The heterogenic final cell cycle of chicken retinal Lim1 horizontal cells is not regulated by the DNA damage response pathway.
Authors: Fard Et al.
Cell Cycle 2013;13:408
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.
J Biol Chem 2013;110:2234
Role of 53BP1 oligomerization in regulating double-strand break repair.
Authors: Lottersberger Et al.
Proc Natl Acad Sci U S A 2013;110:2146
ATM and MET kinases are synthetic lethal with nongenotoxic activation of p53.
Authors: Sullivan Et al.
Proc Natl Acad Sci U S A 2012;8:646
Mechanism-based screen establishes signalling framework for DNA damage-associated G1 checkpoint response.
Authors: Richardson Et al.
PLoS One 2012;7:e31627
PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling.
Authors: Ando Et al.
Mol Cell 2012;47:681
SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response.
Authors: Mund Et al.
Nucleic Acids Res 2012;40:11363
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
Regulation of SIRT1 activity by genotoxic stress.
Authors: Yuan Et al.
Genes Dev 2012;26:791
Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.
Authors: Yamamoto Et al.
J Virol 2012;198:305
Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation.
Authors: Fumagalli Et al.
Nat Cell Biol 2012;14:355
Detection of early Abl kinase activation after ionizing radiation by using a peptide biosensor.
Authors: Tang Et al.
Mol Cell Biol 2012;13:665
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
Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation.
Authors: Klotz-Noack Et al.
J Cell Sci 2012;125:2436
Role for Rif1 in the checkpoint response to damaged DNA in Xenopus egg extracts.
Authors: Kumar Et al.
Cell Cycle 2012;11:1183
Oncolytic virus-mediated manipulation of DNA damage responses: synergy with chemotherapy in killing glioblastoma stem cells.
Authors: Kanai Et al.
J Natl Cancer Inst 2012;104:42
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
γ-Radiation promotes immunological recognition of cancer cells through increased expression of cancer-testis antigens in vitro and in vivo.
Authors: Sharma Et al.
Gene Ther 2011;6:e28217
The phenotypic radiation resistance of CD44+/CD24(-or low) breast cancer cells is mediated through the enhanced activation of ATM signaling.
Authors: Yin and Glass
PLoS One 2011;6:e24080
Differential inhibitor sensitivity between human kinases VRK1 and VRK2.
Authors: Vázquez-Cedeira Et al.
PLoS One 2011;6:e23235
H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes.
Authors: Helmink Et al.
Identification of small molecule inhibitors of phosphatidylinositol 3-kinase and autophagy.
Authors: Farkas Et al.
J Biol Chem 2011;286:38904
Doxorubicin bypasses the cytoprotective effects of eIF2α phosphorylation and promotes PKR-mediated cell death.
Authors: Peidis Et al.
Cell Death Differ 2011;18:145
Differential effects of DNA double-strand break repair pathways on single-strand and self-complementary adeno-associated virus vector genomes.
Authors: Cataldi and McCarty
J Exp Med 2010;84:8673
Selenium compounds activate ATM-dependent DNA damage response via the mismatch repair protein hMLH1 in colorectal cancer cells.
Authors: Qi Et al.
Am J Physiol Cell Physiol 2010;285:33010
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