Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C21H17NO3S2 |
| Molecular Weight | 395.495 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O=C1C=C(OC(=C1)C2=C3SC4=C(SC3=CC=C2)C=CC=C4)N5CCOCC5
InChI
InChIKey=XRKYMMUGXMWDAO-UHFFFAOYSA-N
InChI=1S/C21H17NO3S2/c23-14-12-16(25-20(13-14)22-8-10-24-11-9-22)15-4-3-7-19-21(15)27-18-6-2-1-5-17(18)26-19/h1-7,12-13H,8-11H2
| Molecular Formula | C21H17NO3S2 |
| Molecular Weight | 395.495 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
KU-55933 (2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one) is an ATP-competitive inhibitor of Ataxia telangiectasia mutated (ATM) kinase. Exposure of cells to KU-55933 resulted in a significant sensitization to the cytotoxic effects of ionizing radiation and to the DNA double-strand break-inducing chemotherapeutic agents, etoposide, doxorubicin, and camptothecin. Inhibition of ATM by KU-55933 also caused a loss of ionizing radiation-induced cell cycle arrest. By contrast, KU-55933 did not potentiate the cytotoxic effects of ionizing radiation on ataxia-telangiectasia cells, nor did it affect their cell cycle profile after DNA damage. KU55933 is a hydrophobic molecule and is insoluble in water. Nanoparticle KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC).
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage. | 2005 Dec 16 |
|
| Chronicles in drug discovery. | 2005 Jun |
|
| Features of selective kinase inhibitors. | 2005 Jun |
|
| ATM: HIV-1's Achilles heel? | 2005 May |
|
| Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair. | 2006 |
|
| Emerging cancer therapeutic opportunities target DNA-repair systems. | 2006 Jun |
|
| Pyranone, thiopyranone, and pyridone inhibitors of phosphatidylinositol 3-kinase related kinases. Structure-activity relationships for DNA-dependent protein kinase inhibition, and identification of the first potent and selective inhibitor of the ataxia telangiectasia mutated kinase. | 2007 Apr 19 |
|
| Extracellular signal-related kinase positively regulates ataxia telangiectasia mutated, homologous recombination repair, and the DNA damage response. | 2007 Feb 1 |
|
| Rapid activation of ATM on DNA flanking double-strand breaks. | 2007 Nov |
|
| p21(WAF1/CIP1) induction by 5-azacytosine nucleosides requires DNA damage. | 2008 Jun 5 |
|
| Growth of persistent foci of DNA damage checkpoint factors is essential for amplification of G1 checkpoint signaling. | 2008 Mar 1 |
|
| Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced senescent tumor cells: implications for chemotherapy. | 2008 Mar 15 |
|
| Chk1 and Claspin potentiate PCNA ubiquitination. | 2008 May 1 |
|
| Cadmium-induced adaptive response in cells of Chinese hamster ovary cell lines with varying DNA repair capacity. | 2009 Apr |
|
| Inhibition of ataxia telangiectasia mutated kinase activity enhances TRAIL-mediated apoptosis in human melanoma cells. | 2009 Apr 15 |
|
| ATM-ATR-dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype. | 2009 Apr 9 |
|
| Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner. | 2009 Aug |
|
| Cytotoxic effects of temozolomide and radiation are additive- and schedule-dependent. | 2009 Dec 1 |
|
| Coactivation of ATM/ERK/NF-kappaB in the low-dose radiation-induced radioadaptive response in human skin keratinocytes. | 2009 Jun 1 |
|
| DNA double helix unwinding triggers transcription block-dependent apoptosis: a semiquantitative probe of the response of ATM, RNAPII, and p53 to two DNA intercalators. | 2009 Mar 16 |
|
| DNA damage, signalling and repair after exposure of cells to the sulphur mustard analogue 2-chloroethyl ethyl sulphide. | 2009 Mar 29 |
|
| The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation. | 2009 Nov 10 |
|
| ATM-dependent hyper-radiosensitivity in mammalian cells irradiated by heavy ions. | 2009 Sep 1 |
|
| ATM-dependent and -independent dynamics of the nuclear phosphoproteome after DNA damage. | 2010 Dec 7 |
|
| The ATM inhibitor KU-55933 suppresses cell proliferation and induces apoptosis by blocking Akt in cancer cells with overactivated Akt. | 2010 Jan |
|
| ATM is involved in cell-cycle control through the regulation of retinoblastoma protein phosphorylation. | 2010 May |
|
| DNA damage and DNA damage responses in THP-1 monocytes after exposure to spores of either Stachybotrys chartarum or Aspergillus versicolor or to T-2 toxin. | 2010 May |
|
| Activation of ataxia telangiectasia muted under experimental models and human Parkinson's disease. | 2010 Nov |
|
| ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress. | 2010 Oct 8 |
|
| Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells. | 2010 Sep 1 |
|
| Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil. | 2011 |
|
| Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents. | 2011 Apr 14 |
|
| 5-Methoxyflavanone induces cell cycle arrest at the G2/M phase, apoptosis and autophagy in HCT116 human colon cancer cells. | 2011 Aug 1 |
|
| Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. | 2011 Feb |
|
| Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. | 2011 Oct 30 |
|
| DNA damage-sensing kinases mediate the mouse 2-cell embryo's response to genotoxic stress. | 2011 Sep |
|
| Identification of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel target of bisphenol A. | 2012 |
|
| Dynamic coregulatory complex containing BRCA1, E2F1 and CtIP controls ATM transcription. | 2012 |
|
| The autophagy-senescence connection in chemotherapy: must tumor cells (self) eat before they sleep? | 2012 Dec |
|
| DNA damage responses in cells exposed to sulphur mustard. | 2012 Feb 25 |
|
| The ToxTracker assay: novel GFP reporter systems that provide mechanistic insight into the genotoxic properties of chemicals. | 2012 Jan |
|
| Role of autophagy in chemoresistance: regulation of the ATM-mediated DNA-damage signaling pathway through activation of DNA-PKcs and PARP-1. | 2012 Mar 15 |
|
| Progesterone and DNA damage encourage uterine cell proliferation and decidualization through up-regulating ribonucleotide reductase 2 expression during early pregnancy in mice. | 2012 May 4 |
|
| Clioquinol induces DNA double-strand breaks, activation of ATM, and subsequent activation of p53 signaling. | 2012 Sep 4 |
|
| A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. | 2013 Apr 15 |
|
| Direct activation of ATM by resveratrol under oxidizing conditions. | 2014 |
|
| γ-H2AX is a sensitive marker of DNA damage induced by metabolically activated 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. | 2015 Oct |
|
| Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms. | 2015 Sep 22 |
|
| The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion. | 2016 Feb 1 |
Patents
Sample Use Guides
Mice bearing either H460 or A549 flank xenograft tumors received a 500 ug/kg dose of KU55933 as a free drug formulation or nanoparticle through the tail vein.
Route of Administration:
Intravenous
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 08:34:52 UTC 2023
by
admin
on
Sat Dec 16 08:34:52 UTC 2023
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| Record UNII |
O549494L5D
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| Record Status |
Validated (UNII)
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| Record Version |
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587871-26-9
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5278396
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| Related Record | Type | Details | ||
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