Home / ATM and ATR Kinase Inhibitors / KU 55933

KU 55933

Catalog #: 3544
97 Citations Datasheet
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3544/10
KU 55933 | CAS No. 587871-26-9 | ATM and ATR Kinase Inhibitors
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Description: Potent and selective ATM kinase inhibitor

Chemical Name: 2-(4-Morpholinyl)-6-(1-thianthrenyl)-4H-pyran-4-one

Purity: ≥98%

Product Details
Citations (97)
Reviews
Biological Activity Technical Data Background Product Datasheets Calculators

Biological Activity

KU 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.

Technical Data

M.Wt:
395.49
Formula:
C21H17NO3S2
Solubility:
Soluble to 100 mM in DMSO and to 50 mM in ethanol
Purity:
≥98%
Storage:
Desiccate at -20°C
CAS No:
587871-26-9

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.

Background References

  1. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM.
    Hickson I, Zhao Y, Richardson CJ et al.
    Cancer Res
  2. Regulation of SIRT1 activity by genotoxic stress.
    Yuan J, Luo K, Liu T
    Genes Dev., 2012;26(8):791-6.
  3. Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXRgamma activation.
    Leung W, Vong Q, Lin W, Janke L, Chen T, Leung W
    J Exp Med, 2013;210(12):2675-92.
  4. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation.
    Fumagalli M, Rossiello F, Clerici M
    Nat. Cell Biol., 2012;14(4):355-65.
  5. ROS-dependent activation of JNK converts p53 into an efficient inhibitor of oncogenes leading to robust apoptosis.
    Shi Y, Nikulenkov F, Zawacka-Pankau J, Li H, Gabdoulline R, Xu J, Eriksson S, Hedstrom E, Issaeva N, Kel A, Arner E, Selivanova G
    Cell Death Differ, 2014;21(4):612-23.
  6. NADPH oxidase 4 is a critical mediator in Ataxia telangiectasia disease.
    Weyemi, Urbain, Redon, Christop, Aziz, Towqir, Choudhuri, Rohini, Maeda, Daisuke, Parekh, Palak R, Bonner, Michael, Arbiser, Jack L, Bonner, William
    Proc Natl Acad Sci U S A, 2015;112(7):2121-6.
  7. Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation.

    J. Cell. Sci., 2012;125(0):2436-45.
  8. NOX2-dependent ATM kinase activation dictates pro-inflammatory macrophage phenotype and improves effectiveness to radiation therapy
    Q Wu, A Allouch, A Paoletti, C Leteur, C Mirjolet, I Martins, L Voisin, F Law, H Dakhli, E Mintet, M Thoreau, Z Muradova, M Gauthier, O Caron, F Milliat, DM Ojcius, F Rosselli, E Solary, N Modjtahedi, E Deutsch, JL Perfettini
    Cell Death Differ., 2017;0(0):.
  9. The scaffold protein WRAP53beta orchestrates the ubiquitin response critical for DNA double-strand break repair.
    Henriksson S, Rassoolzadeh H, Hedstrom E, Coucoravas C, Julner A, Goldstein M, Imreh G, Zhivotovsky B, Kastan M, Helleday T, Farnebo M
    Genes Dev, 2014;28(24):2726-38.
  10. BRD4 inhibitors block telomere elongation
    S Wang, AM Pike, SS Lee, MA Strong, CJ Connelly, CW Greider
    Nucleic Acids Res., 2017;45(14):8403-8410.
  11. Cell cycle-regulated ubiquitination of tankyrase 1 by RNF8 and ABRO1/BRCC36 controls the timing of sister telomere resolution
    Ekta Tripathi
    EMBO J, 2016;0(0):.
  12. The CHD6 chromatin remodeler is an oxidative DNA damage response factor
    S Moore, ND Berger, MS Luijsterbu, CG Piett, FKT Stanley, CU Schräder, S Fang, JA Chan, DC Schriemer, ZD Nagel, H van Attiku, AA Goodarzi
    Nat Commun, 2019;10(1):241.
  13. 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
  14. Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis.
    Eaton et al.
    J.Clin.Invest., 2007;117:2723

Product Datasheets

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Citations for KU 55933

The citations listed below are publications that use Tocris products. Selected citations for KU 55933 include:

97 Citations: Showing 1 - 10

  1. Citrate Promotes Excessive Lipid Biosynthesis and Senescence in Tumor Cells for Tumor Therapy.
    Authors: Xia Et al.
    Adv Sci (Weinh)  2022;9:e2101553
  2. High replication stress and limited Rad51-mediated DNA repair capacity, but not oxidative stress, underlie oligodendrocyte precursor cell radiosensitivity.
    Authors: Jennifer A Et al.
    NAR Cancer  2022;4:zcac012
  3. Dual signaling via interferon and DNA damage response elicits entrapment by giant PML nuclear bodies.
    Authors: Regina Et al.
    Elife  2022;11
  4. HCV Activates Somatic L1 Retrotransposition-A Potential Hepatocarcinogenesis Pathway.
    Authors: John Et al.
    Cancers (Basel)  2021;13
  5. A robust CRISPR-Cas9-based fluorescent reporter assay for the detection and quantification of DNA double-strand break repair.
    Authors: Tarek Et al.
    Nucleic Acids Res  2020;48:e126
  6. Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response.
    Authors: Rosina Et al.
    Sci Rep  2019;9:5447
  7. Autophagy is essential for oligodendrocyte differentiation, survival, and proper myelination.
    Authors: Russell M Et al.
    Glia  2019;67:1745-1759
  8. E3 Ubiquitin Ligases RNF20 and RNF40 Are Required for Double-Stranded Break (DSB) Repair: Evidence for Monoubiquitination of Histone H2B Lysine 120 as a Novel Axis of DSB Signaling and Repair.
    Authors: Alberto Et al.
    Mol Cell Biol  2019;39
  9. RAG-Mediated DNA Breaks Attenuate PU.1 Activity in Early B Cells through Activation of a SPIC-BCLAF1 Complex.
    Authors: Kenneth M Et al.
    Cell Rep  2019;29:829-843.e5
  10. Transient inhibition of p53 homologs protects ovarian function from two distinct apoptotic pathways triggered by anticancer therapies.
    Authors: So-Youn Et al.
    Cell Death Differ  2019;26:502-515
  11. 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.
    Neoplasia  2019;21:30
  12. Cytotoxic and Antitumor Activity of Lactaptin in Combination with Autophagy Inducers and Inhibitors.
    Authors: Bagamanshina Et al.
    Biomed Res Int  2019;2019:4087160
  13. Autophagy is required for lung development and morphogenesis.
    Authors: Yeganeh Et al.
    J Clin Invest  2019;130:2904
  14. 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
  15. Typhoid toxin exhausts the RPA response to DNA replication stress driving senescence and Salmonella infection.
    Authors: Ibler Et al.
    Nat Commun  2019;10:4040
  16. The CHD6 chromatin remodeler is an oxidative DNA damage response factor.
    Authors: Moore Et al.
    Nat Commun  2019;10:241
  17. 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
  18. 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.
    F1000Res  2018;7:1233
  19. The Histone Chaperone FACT Coordinates H2A.X-Dependent Signaling and Repair of DNA Damage.
    Authors: Piquet Et al.
    Mol Cell  2018;72:888
  20. The Chromatin Reader ZMYND8 Regulates Igh Enhancers to Promote Immunoglobulin Class Switch Recombination.
    Authors: Delgado-Benito Et al.
    Mol Cell  2018;72:636
  21. Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders.
    Authors: Calo Et al.
    Nature  2018;554:112
  22. Cell type-dependent bimodal p53 activation engenders a dynamic mechanism of chemoresistance.
    Authors: Yang Et al.
    Sci Adv  2018;4:eaat5077
  23. Dppa2/4 Facilitate Epigenetic Remodeling during Reprogramming to Pluripotency.
    Authors: Thomas A Et al.
    Cell Stem Cell  2018;23:396-411.e8
  24. SETD2-dependent H3K36me3 plays a critical role in epigenetic regulation of the HPV31 life cycle.
    Authors: Gautam Et al.
    PLoS Pathog  2018;14:e1007367
  25. Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy.
    Authors: Benkafadar Et al.
    EMBO Mol Med  2017;9:7
  26. Nuclear Acetyl-CoA Production by ACLY Promotes Homologous Recombination.
    Authors: Jingwen Et al.
    Mol Cell  2017;67:252-265.e6
  27. Regulation of human polλ by ATM-mediated phosphorylation during non-homologous end joining.
    Authors: Dale A Et al.
    DNA Repair (Amst)  2017;51:31-45
  28. ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration.
    Authors: Jaiswal Et al.
    EMBO J  2017;36:2161
  29. 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
  30. Drug-induced hyperploidy stimulates an antitumor NK cell response mediated by NKG2D and DNAM-1 receptors.
    Authors: Acebes-Huerta Et al.
    Oncoimmunology  2016;5:e1074378
  31. 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
  32. Fe65 Is Phosphorylated on Ser289 after UV-Induced DNA Damage.
    Authors: Langlands Et al.
    PLoS One  2016;11:e0155056
  33. Activation of DNA Damage Response Pathways during Lytic Replication of KSHV.
    Authors: Hollingworth Et al.
    Mol Cell Biol  2015;7:2908
  34. Selective Inhibition of Parallel DNA Damage Response Pathways Optimizes Radiosensitization of Glioblastoma Stem-like Cells.
    Authors: Ahmed Et al.
    Cancer Res  2015;75:4416
  35. 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
  36. 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
  37. 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.
    Viruses  2015;5:140156
  38. 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
  39. 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.
    Toxicology  2015;331:35
  40. Spatio-temporal regulation of RAG2 following genotoxic stress.
    Authors: Rodgers Et al.
    DNA Repair (Amst)  2015;27:19
  41. Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage.
    Authors: Gibbs-Seymour Et al.
    Open Biol  2015;14:162
  42. 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
  43. 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
  44. 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
  45. Inactivation of p53 in Human Keratinocytes Leads to Squamous Differentiation and Shedding via Replication Stress and Mitotic Slippage.
    Authors: Alberto Et al.
    Cell Rep  2014;9:1349-60
  46. TLR8 signaling enhances tumor immunity by preventing tumor-induced T-cell senescence.
    Authors: Ye Et al.
    EMBO Mol Med  2014;6:1294
  47. SMAR1 coordinates HDAC6-induced deacetylation of Ku70 and dictates cell fate upon irradiation.
    Authors: Chaudhary Et al.
    Cell Death Dis  2014;5:e1447
  48. ATM specifically mediates repair of double-strand breaks with blocked DNA ends.
    Authors: Alvarez-Quilón Et al.
    Nat Commun  2014;5:3347
  49. 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
  50. PARP-1 dependent recruitment of the amyotrophic lateral sclerosis-associated protein FUS/TLS to sites of oxidative DNA damage.
    Authors: Majid Et al.
    Nucleic Acids Res  2014;42:307-14
  51. 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
  52. The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair.
    Authors: Henriksson Et al.
    Genes Dev  2014;28:2726
  53. Selenoprotein H suppresses cellular senescence through genome maintenance and redox regulation.
    Authors: Wu Et al.
    J Biol Chem  2014;289:34378
  54. Preconditioning stimuli induce autophagy via sphingosine kinase 2 in mouse cortical neurons.
    Authors: Sheng Et al.
    Oncotarget  2014;289:20845
  55. N-nitroso-N-ethylurea activates DNA damage surveillance pathways and induces transformation in mammalian cells.
    Authors: Satish Et al.
    BMC Cancer  2014;14:287
  56. 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
  57. Repair of DNA strand breaks in a minichromosome in vivo: kinetics, modeling, and effects of inhibitors.
    Authors: Ronald Et al.
    PLoS One  2013;8:e52966
  58. SMC1-mediated intra-S-phase arrest facilitates bocavirus DNA replication.
    Authors: Luo Et al.
    J Virol  2013;87:4017
  59. Human papillomavirus episome stability is reduced by aphidicolin and controlled by DNA damage response pathways.
    Authors: Edwards Et al.
    J Virol  2013;87:3979
  60. Targeting XRCC1 deficiency in breast cancer for personalized therapy.
    Authors: Sultana Et al.
    Cancer Res  2013;73:1621
  61. 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
  62. 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
  63. 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
  64. Mechanism of DNA resection during intrachromosomal recombination and immunoglobulin class switching.
    Authors: Bothmer Et al.
    Chembiochem  2013;210:115
  65. Hairpin-end conformation of adeno-associated virus genome determines interactions with DNA-repair pathways.
    Authors: Cataldi and McCarty
    J Biol Chem  2013;20:686
  66. Ionizing radiation enhances dl922-947-mediated cell death of anaplastic thyroid carcinoma cells.
    Authors: Passaro Et al.
    Endocr Relat Cancer  2013;20:633
  67. 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
  68. E1a promotes c-Myc-dependent replicative stress: implications in glioblastoma radiosensitization.
    Authors: Valero Et al.
    Cell Cycle  2013;13:52
  69. 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
  70. 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
  71. Role of 53BP1 oligomerization in regulating double-strand break repair.
    Authors: Lottersberger Et al.
    Proc Natl Acad Sci U S A  2013;110:2146
  72. 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
  73. Mechanism-based screen establishes signalling framework for DNA damage-associated G1 checkpoint response.
    Authors: Richardson Et al.
    PLoS One  2012;7:e31627
  74. PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling.
    Authors: Ando Et al.
    Mol Cell  2012;47:681
  75. 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
  76. 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
  77. Regulation of SIRT1 activity by genotoxic stress.
    Authors: Yuan Et al.
    Genes Dev  2012;26:791
  78. Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.
    Authors: Yamamoto Et al.
    J Virol  2012;198:305
  79. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation.
    Authors: Fumagalli Et al.
    Nat Cell Biol  2012;14:355
  80. Detection of early Abl kinase activation after ionizing radiation by using a peptide biosensor.
    Authors: Tang Et al.
    Mol Cell Biol  2012;13:665
  81. 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
  82. 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
  83. Preclinical development of the novel Chk1 inhibitor SCH900776 in combination with DNA-damaging agents and antimetabolites.
    Authors: Alan Et al.
    Mol Cancer Ther  2012;11:427-38
  84. Role for Rif1 in the checkpoint response to damaged DNA in Xenopus egg extracts.
    Authors: Kumar Et al.
    Cell Cycle  2012;11:1183
  85. 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
  86. 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
  87. 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
  88. 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
  89. Differential inhibitor sensitivity between human kinases VRK1 and VRK2.
    Authors: Vázquez-Cedeira Et al.
    PLoS One  2011;6:e23235
  90. H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes.
    Authors: Helmink Et al.
    Nature  2011;469:245
  91. Identification of small molecule inhibitors of phosphatidylinositol 3-kinase and autophagy.
    Authors: Farkas Et al.
    J Biol Chem  2011;286:38904
  92. Abrogation of Wip1 expression by RITA-activated p53 potentiates apoptosis induction via activation of ATM and inhibition of HdmX.
    Authors: H Et al.
    Cell Death Differ  2011;18:1736-45
  93. Doxorubicin bypasses the cytoprotective effects of eIF2α phosphorylation and promotes PKR-mediated cell death.
    Authors: Peidis Et al.
    Cell Death Differ  2011;18:145
  94. An ataxia-telangiectasia-mutated (ATM) kinase mediated response to DNA damage down-regulates the mRNA-binding potential of THOC5.
    Authors: Anthony D Et al.
    RNA  2011;17:1957-66
  95. 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
  96. 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
  97. DNA damage-mediated induction of a chemoresistant niche.
    Authors: Michael T Et al.
    Cell  2010;143:355-66

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