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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.
|Storage||Desiccate at -20°C|
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.
|Solvent||Max Conc. mg/mL||Max Conc. mM|
Preparing Stock Solutions
The following data is based on the product molecular weight 395.49. 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|
|1 mM||2.53 mL||12.64 mL||25.29 mL|
|5 mM||0.51 mL||2.53 mL||5.06 mL|
|10 mM||0.25 mL||1.26 mL||2.53 mL|
|50 mM||0.05 mL||0.25 mL||0.51 mL|
References are publications that support the biological activity of the product.
Hickson et al (2004) Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res. 64 9152 PMID: 15604286
Eaton et al (2007) Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis. J.Clin.Invest. 117 2723 PMID: 17786248
Crescenzi et al (2008) Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced senescent tumor cells: implications for chemotherapy. Clin.Cancer Res. 14 1877 PMID: 18347191
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Keywords: KU 55933, KU 55933 supplier, Potent, selective, ATM, kinase, inhibitors, inhibits, Ataxia, Telangiectasia, Mutated, Kinase, Kinases, KU55933, &, ATR, Checkpoint, Control, 3544, Tocris Bioscience
60 Citations for KU 55933
Citations are publications that use Tocris products. Selected citations for KU 55933 include:
Allen et al (2015) DNA Damage Response Proteins and Oxygen Modulate Prostaglandin E2 Growth Factor Release in Response to Low and High LET Ionizing Radiation. Front Oncol 5 260 PMID: 26697402
Ahmed et al (2015) Selective Inhibition of Parallel DNA Damage Response Pathways Optimizes Radiosensitization of Glioblastoma Stem-like Cells. Cancer Res 75 4416 PMID: 26282173
Rodgers et al (2015) Spatio-temporal regulation of RAG2 following genotoxic stress. DNA Repair (Amst) 27 19 PMID: 25625798
Beggs et al (2015) 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. Toxicology 331 35 PMID: 25748550
Peidis et al (2011) Doxorubicin bypasses the cytoprotective effects of eIF2α phosphorylation and promotes PKR-mediated cell death. Cell Death Differ 18 145 PMID: 20559319
Helmink et al (2011) H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes. Nature 469 245 PMID: 21160476
Benkafadar et al (2017) Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy. EMBO Mol Med 9 7 PMID: 27794029
Okita et al (2015) 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. PLoS One 10 e0139809 PMID: 26439264
Teng et al (2015) Pharmacologic inhibition of ATR and ATM offers clinically important distinctions to enhancing platinum or radiation response in ovarian, endometrial, and cervical cancer cells. Gynecol Oncol 136 554 PMID: 25560806
Sheng et al (2014) Preconditioning stimuli induce autophagy via sphingosine kinase 2 in mouse cortical neurons. Oncotarget 289 20845 PMID: 24928515
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. J Biol Chem 110 2234 PMID: 23345432
Bothmer et al (2013) Mechanism of DNA resection during intrachromosomal recombination and immunoglobulin class switching. Chembiochem 210 115 PMID: 23254285
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
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
Yin and Glass (2011) The phenotypic radiation resistance of CD44+/CD24(-or low) breast cancer cells is mediated through the enhanced activation of ATM signaling. PLoS One 6 e24080 PMID: 21935375
Vázquez-Cedeira et al (2011) Differential inhibitor sensitivity between human kinases VRK1 and VRK2. PLoS One 6 e23235 PMID: 21829721
Farkas et al (2011) Identification of small molecule inhibitors of phosphatidylinositol 3-kinase and autophagy. J Biol Chem 286 38904 PMID: 21930714
Sharma et al (2011) γ-Radiation promotes immunological recognition of cancer cells through increased expression of cancer-testis antigens in vitro and in vivo. Gene Ther 6 e28217 PMID: 22140550
Wu et al (2014) Selenoprotein H suppresses cellular senescence through genome maintenance and redox regulation. J Biol Chem 289 34378 PMID: 25336634
Sakai et al (2014) Wild-type p53-induced phosphatase 1 (Wip1) forestalls cellular premature senescence at physiological oxygen levels by regulating DNA damage response signaling during DNA replication. Cell Cycle 13 1015 PMID: 24552809
Kim and Suh (2014) Defying DNA double-strand break-induced death during prophase I meiosis by temporal TAp63α phosphorylation regulation in developing mouse oocytes. Mol Cell Biol 34 1460 PMID: 24515437
Alekseev et al (2014) Inhibition of ataxia telangiectasia mutated (ATM) kinase suppresses herpes simplex virus type 1 (HSV-1) keratitis. Invest Ophthalmol Vis Sci 55 706 PMID: 24370835
Tang et al (2012) Detection of early Abl kinase activation after ionizing radiation by using a peptide biosensor. Mol Cell Biol 13 665 PMID: 22334513
Sullivan et al (2012) ATM and MET kinases are synthetic lethal with nongenotoxic activation of p53. Proc Natl Acad Sci U S A 8 646 PMID: 22660439
Yamamoto et al (2012) Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice. J Virol 198 305 PMID: 22869596
Qi et al (2010) Selenium compounds activate ATM-dependent DNA damage response via the mismatch repair protein hMLH1 in colorectal cancer cells. Am J Physiol Cell Physiol 285 33010 PMID: 20709753
Acebes-Huerta et al (2016) Drug-induced hyperploidy stimulates an antitumor NK cell response mediated by NKG2D and DNAM-1 receptors. Oncoimmunology 5 e1074378 PMID: 27057443
Langlands et al (2016) Fe65 Is Phosphorylated on Ser289 after UV-Induced DNA Damage. PLoS One 11 e0155056 PMID: 27176072
Sultana et al (2013) Targeting XRCC1 deficiency in breast cancer for personalized therapy. Cancer Res 73 1621 PMID: 23253910
Passaro et al (2013) Ionizing radiation enhances dl922-947-mediated cell death of anaplastic thyroid carcinoma cells. Endocr Relat Cancer 20 633 PMID: 23839822
Valero et al (2013) E1a promotes c-Myc-dependent replicative stress: implications in glioblastoma radiosensitization. Cell Cycle 13 52 PMID: 24196438
Luo et al (2013) SMC1-mediated intra-S-phase arrest facilitates bocavirus DNA replication. J Virol 87 4017 PMID: 23365434
Mund et al (2012) SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response. Nucleic Acids Res 40 11363 PMID: 23034801
Richardson et al (2012) Mechanism-based screen establishes signalling framework for DNA damage-associated G1 checkpoint response. PLoS One 7 e31627 PMID: 22384045
Klotz-Noack et al (2012) Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation. J Cell Sci 125 2436 PMID: 22366459
Fumagalli et al (2012) Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat Cell Biol 14 355 PMID: 22426077
Yuan et al (2012) Regulation of SIRT1 activity by genotoxic stress. Genes Dev 26 791 PMID: 22465953
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. J Exp Med 84 8673 PMID: 20538857
Cataldi and McCarty (2013) Hairpin-end conformation of adeno-associated virus genome determines interactions with DNA-repair pathways. J Biol Chem 20 686 PMID: 23151519
Montané and Menand (2013) ATP-competitive mTOR kinase inhibitors delay plant growth by triggering early differentiation of meristematic cells but no developmental patterning change. Nat Chem Biol 64 4361 PMID: 23963679
Lottersberger et al (2013) Role of 53BP1 oligomerization in regulating double-strand break repair. Proc Natl Acad Sci U S A 110 2146 PMID: 23345425
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
Fard et al (2013) The heterogenic final cell cycle of chicken retinal Lim1 horizontal cells is not regulated by the DNA damage response pathway. Cell Cycle 13 408 PMID: 24247150
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
Kanai et al (2012) Oncolytic virus-mediated manipulation of DNA damage responses: synergy with chemotherapy in killing glioblastoma stem cells. J Natl Cancer Inst 104 42 PMID: 22173583
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
Kumar et al (2012) Role for Rif1 in the checkpoint response to damaged DNA in Xenopus egg extracts. Cell Cycle 11 1183 PMID: 22391207
Ando et al (2012) PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling. Mol Cell 47 681 PMID: 22854598
Liu et al (2015) A radiosensitivity MiRNA signature validated by the TCGA database for head and neck squamous cell carcinomas. Aging Cell 6 34649 PMID: 26452218
Gibbs-Seymour et al (2015) Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage. Open Biol 14 162 PMID: 25645366
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. Mol Cell Biol 7 2908 PMID: 26057167
Stechow et al (2015) The E3 ubiquitin ligase ARIH1 protects against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest. Proc Natl Acad Sci U S A 35 1254 PMID: 25624349
Malonia et al (2015) F-box protein FBXO31 directs degradation of MDM2 to facilitate p53-mediated growth arrest following genotoxic stress. J Cell Biol 112 8632 PMID: 26124108
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
Alvarez-Quilón et al (2014) ATM specifically mediates repair of double-strand breaks with blocked DNA ends. Nat Commun 5 3347 PMID: 24572510
Ye et al (2014) TLR8 signaling enhances tumor immunity by preventing tumor-induced T-cell senescence. EMBO Mol Med 6 1294 PMID: 25231413
Chaudhary et al (2014) SMAR1 coordinates HDAC6-induced deacetylation of Ku70 and dictates cell fate upon irradiation. Cell Death Dis 5 e1447 PMID: 25299772
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Literature in this Area
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Cell Cycle & DNA Damage Repair Poster
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. Adapted from the 2015 Cancer Product Guide, Edition 3, 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.