| Identification | Back Directory | [Name]
KU 60019 | [CAS]
925701-46-8 | [Synonyms]
KU-60019
(KU60019
2-((2R,6S)-2,6-Dimethylmorpholino)-N-(5-(6-morpholino-4-oxo-4H-pyran-2-yl)-9H-thioxanthen-2-yl
2-((2R,6S)-2,6-Dimethylmorpholino)-N-(5-(6-morpholino-4-oxo-4H-pyran-2-yl)-9H-thioxanthen-2-yl)acetamide
(2R,6S)-rel-2,6-Dimethyl-N-[5-[6-(4-morpholinyl)-4-oxo-4H-pyran-2-yl]-9H-thioxanthen-2-yl]-4-morpholineacetamide
4-Morpholineacetamide, 2,6-dimethyl-N-[5-[6-(4-morpholinyl)-4-oxo-4H-pyran-2-yl]-9H-thioxanthen-2-yl]-, (2R,6S)-rel- | [Molecular Formula]
C30H33N3O5S | [MDL Number]
MFCD18384974 | [MOL File]
925701-46-8.mol | [Molecular Weight]
547.67 |
| Chemical Properties | Back Directory | [Boiling point ]
786.6±60.0 °C(Predicted) | [density ]
1.314±0.06 g/cm3 (20 ºC 760 Torr) | [storage temp. ]
Store at -20°C | [solubility ]
DMF:20.0(Max Conc. mg/mL);36.52(Max Conc. mM)
DMF:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);0.91(Max Conc. mM)
DMSO:75.0(Max Conc. mg/mL);136.94(Max Conc. mM)
Ethanol:50.0(Max Conc. mg/mL);91.3(Max Conc. mM) | [form ]
A crystalline solid | [pka]
13.52±0.20(Predicted) | [color ]
Light yellow to khaki |
| Hazard Information | Back Directory | [Description]
Ataxia-telangiectasia mutated (ATM) is a serine/threonine kinase that activates checkpoint signaling following double strand DNA breaks and genotoxic stress. Ku-60019 is a potent, reversible inhibitor of ATM kinase (IC50 = 6.3 nM), blocking the phosphorylation of ATM substrate proteins. It is much less effective or without effect against a panel of 229 other kinases. Ku-60019 sensitizes glioma cells to radiation and inhibits migration and invasion of glioma cells in vitro. It produces radiosensitization and increases survival in vivo when administered intra-tumorally in orthotopic xenograft models of glioblastoma multiforme. Ku-60019 is particularly effective in producing lethality in cells with mutant p53 or that are deficient in PTEN. | [Uses]
KU-60019 is a potent and reversible inhibitor of ATM kinase, blocking the phosphorylation of ATM substrate proteins. It sensitizes glioma cells to radiation and inhibits migration and invasion of glioma cells in vitro. | [in vivo]
Despite PTEN-deficient control tumors reaching a 4-fold increase in size before PTEN wild-type controls, KU-60019-treated PTEN-deficient tumors display a statistically significant slowing in growth. This growth inhibition is especially evident at the start of the experiment (days 5-12) just after KU-60019 is administered (days 1-5)[2]. | [IC 50]
ATM: 6.3 nM (IC50); DNA-PKcs: 1.7 μM (IC50) | [References]
[1] SARAH E GOLDING. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion.[J]. Molecular Cancer Therapeutics, 2009: 2894-2902. DOI: 10.1158/1535-7163.mct-09-0519
[2] SARAH E GOLDING. Dynamic inhibition of ATM kinase provides a strategy for glioblastoma multiforme radiosensitization and growth control.[J]. Cell Cycle, 2012, 11 6: 1167-1173. DOI: 10.4161/cc.11.6.19576
[3] LAURA BIDDLESTONE-THORPE. ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation.[J]. Clinical Cancer Research, 2013, 19 12: 3189-3200. DOI: 10.1158/1078-0432.ccr-12-3408
[4] NUALA MCCABE. Mechanistic Rationale to Target PTEN-Deficient Tumor Cells with Inhibitors of the DNA Damage Response Kinase ATM.[J]. Cancer research, 2015: 2159-2165. DOI: 10.1158/0008-5472.can-14-3502 |
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| Company Name: |
Musechem
|
| Tel: |
+1-800-259-7612 |
| Website: |
www.musechem.com |
| Company Name: |
Energy Chemical
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| Tel: |
021-58432009 400-005-6266 |
| Website: |
http://www.energy-chemical.com |
| Company Name: |
ChemeGen
|
| Tel: |
18818260767 |
| Website: |
https://www.chemegen.com |
|