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 |
|
| ATM: HIV-1's Achilles heel? | 2005 May |
|
| Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase. | 2005 May |
|
| Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair. | 2006 |
|
| Extracellular signal-related kinase positively regulates ataxia telangiectasia mutated, homologous recombination repair, and the DNA damage response. | 2007 Feb 1 |
|
| 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 |
|
| 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 |
|
| Cytotoxic effects of temozolomide and radiation are additive- and schedule-dependent. | 2009 Dec 1 |
|
| Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells. | 2010 Sep 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 |
|
| 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 |
|
| Direct activation of ATM by resveratrol under oxidizing conditions. | 2014 |
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 GMT 2023
by
admin
on
Sat Dec 16 08:34:52 GMT 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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| Related Record | Type | Details | ||
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