Basic information Description Features In vitro In vivo Safety Supplier Related
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KU-60019

Basic information Description Features In vitro In vivo Safety Supplier Related

KU-60019 Basic information

Product Name:
KU-60019
Synonyms:
  • KU-60019
  • (2R,6S)-2,6-Dimethyl-N-[5-[6-(4-morpholinyl)-4-oxo-4H-pyran-2-yl]-9H-thioxanthen-2-yl]-4-morpholineacetamide
  • 2-((2S,6R)-2,6-dimethylmorpholino)-N-(5-(6-morpholino-4-oxo-4H-pyran-2-yl)-9H-thioxanthen-2-yl)acetamide
  • KU-60019 (2R,6S)-2,6-Dimethyl-N-[5-[6-(4-morpholinyl)-4-oxo-4H-pyran-2-yl]-9H-thioxanthen-2-yl]-4-morpholineacetamide
  • KU-60019, 925701-49-1
  • KU-60019;KU60019;KU 60019
  • 2-[(2S,6R)-2,6-dimethylmorpholin-4-yl]-N-[5-(6-morpholin-4-yl-4-oxopyran-2-yl)-9H-thioxanthen-2-yl]acetamide
  • CS-444
CAS:
925701-49-1
MF:
C30H33N3O5S
MW:
547.66512
Product Categories:
  • Inhibitors
Mol File:
925701-49-1.mol
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KU-60019 Chemical Properties

Density 
1.314
storage temp. 
-20°C
form 
powder
color 
white to beige
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KU-60019 Usage And Synthesis

Description

KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer.

Features

Improved analog of KU-55933, and is more effective at blocking ATM-mediated DDR events.

In vitro

Compared to KU-55933, KU-60019 is an improved more water-soluble inhibitor of the ATM kinase, while displaying similar target selectivity. KU-60019 has little activity against DNA-PKcs and ATR with IC50 values of 1.7 μM and >10 μM, respectively, as well as 229 other protein kinases such as PI3K, mTOR and mTOR/FKBP12. KU-60019 displays 3- to 10-fold more potency than KU-55933 at blocking radiation-induced phosphorylation of key ATM protein targets such as p53, γ-H2AX, and CHK2, in human glioma U87 and U1242 cells, as 1 μM of KU-60019 significantly induces >70% decrease of p53 (S15) phosphorylation to which extent ~10 μM of KU-55933 is required to achieve. KU-60019 effectively radiosensitizes human glioma cells with dose-enhancement ratio of 1.7 and 4.4 at 1 μM and 10 μM, respectively, and also radiosensitizes the normal fibroblasts but not the A-T fibroblasts. KU-60019 treatment (3 μM) blocks basal and insulin-induced AKT S473 phosphorylation by 70% and ~50%, respectively, and completely reduces radiation-induced AKT phosphorylation below the level of control. The effect of KU-60019 on AKT S473 phosphorylation can be seen in glioma cell lines and normal fibroblasts but not in A-T (h-TERT) cells, and can be significantly blocked by phosphatase inhibitor okadaic acid, suggesting a critical role of ATM kinase in regulating AKT phosphorylation via unknown phosphatase. Consistent with the inhibition of prosurvival AKT signaling, KU-60019 at 3 μM significantly inhibits migration and invasion of human glioma U87 cells by >70% and ~60%, respectively, as well as U1242 cells by >50% and ~60% respectively.

In vivo

In orthotopic glioma U1242/luc-GFP xenograft models, the combination of KU-60019 and radiation significantly increases survival of mice than KU-60019 alone, radiation alone, or no treatment. In addition, p53-mutant gliomas is much more sensitive to KU-60019 radiosensitization than wild-type glioma.

Uses

KU-60019 has been used to block ataxia telangiectasia mutated (ATM), to study its association of with the regulation of H2AX (H2A histone family, member X) and apoptosis inducing factor (AIF)-mediated cell death.

Biochem/physiol Actions

KU-60019 is a potent inhitor of ATM (ataxia telangiectasia mutated) kinase, a member of phosphatidylinositol-3-kinase-related kinase family that is critical in regulating cell cycle checkpoints and DNA repair. KU-60019 has an IC50 value of 6.3 nM. KU-60019 radiosensitizes U1242 human glioma cells, and also blocks U1242 cell migration and invasion through matrigel.

KU-60019Supplier

Shanghai Boyle Chemical Co., Ltd.
Tel
Email
sales@boylechem.com
Products Intro
Product Name:KU-60019
CAS:925701-49-1
Chembest Research Laboratories Limited
Tel
021-20908456
Email
sales@BioChemBest.com
Products Intro
Product Name:KU-60019
CAS:925701-49-1
Remarks:C14648
BeiJing Hwrk Chemicals Limted
Tel
0757-86329057 18516978288
Email
sales.gd@hwrkchemical.com
Products Intro
Product Name:KU-60019
CAS:925701-49-1
Purity:98.00% Package:1g
Jinan Trio PharmaTech Co., Ltd.
Tel
+86 (531) 88811783
Email
sales@trio-pharmatech.com (International market)
Products Intro
Product Name:KU-60019
CAS:925701-49-1
Purity:99% Package:5Mg, 10Mg, 20Mg, 50Mg
Dalian Meilun Biotech Co., Ltd.
Tel
0411-62910999 13889544652
Email
sales@meilune.com
Products Intro
Product Name:KU-60019
CAS:925701-49-1
Purity:>98%,ATM Package:100MG
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