Home DNA Damage/DNA Repair ATM/ATR inhibitor KU-60019 For research use only.

KU-60019

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.

KU-60019 Chemical Structure

KU-60019 Chemical Structure

CAS No. 925701-49-1

Purity & Quality Control

KU-60019 Related Products

Signaling Pathway

ATM/ATR Signaling Pathways

ATM/ATR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BAECs Function Assay 10 μM 1 h  DMSO abolishes the phosphorylation of ATM-Ser1981 25498542
BAECs Function Assay 10 μM 1 h  DMSO inhibits the increase in NOS activity 25498542
U1242 Kinase Assay 3 μM  0.5 h DMSO inhibits the ATM kinase 23620409
U87 Kinase Assay 3 μM  0.5 h DMSO inhibits the ATM kinase 23620409
U1242 Apoptosis Assay 3 μM  1 h  DMSO radiosensitizes human glioma cells 23620409
U87 Apoptosis Assay 3 μM  1 h  DMSO radiosensitizes human glioma cells 23620409
U1242  Kinase Assay 0.01-3 μM  1 h DMSO blocks ATM kinase activity at low concentrations 22370485
glioma Function assay Inhibition of ATM kinase in human glioma cells, IC50 = 0.006 μM. 25387153
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
Click to View More Cell Line Experimental Data

Biological Activity

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.
Targets
ATM [1]
(Cell-free assay)
6.3 nM
In vitro
In vitro

Compared to KU-55933, KU-60019 is an improved 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. [1]
Cell Research Cell lines U87 and U1242
Concentrations Dissolved in water, final concentrations ~3 μM
Incubation Time 1, 3, and 5 days
Method

Cells are exposed to KU-60019 for 1, 3, and 5 days. Cell growth is determined by AlamarBlue. AlamarBlue is added to the medium to the recommended final concentration. Plates are incubated for 1 hour at 37 °C, fluorescence is determined on a Fluoro-Count plate reader (excitation 530 nm, emission 590 nm), and values are taken as a measure of cell growth. Cell survival is determined by trypan blue/fluorescence activated cell sorting (FACS) assay.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-ATM / ATM / p-AKT / AKT / PKM2 30799198
Immunofluorescence GLUT1 30799198
In Vivo
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. [2]
Animal Research Animal Models Athymic female mice harboring orthotopic glioma U1242/luc-GFP tumors or human glioma U1242/luc-GFP tumors
Dosages KU-60019 (10 μM) is delivered at a rate of 0.5 μL/h by osmotic pump; KU-60019 (250 μM) in 12.5 μL is infused by CED.
Administration Administered intratumorally by convection-enhanced delivery or osmotic pump

Chemical Information & Solubility

Molecular Weight 547.67 Formula

C30H33N3O5S
CAS No. 925701-49-1 SDF Download KU-60019 SDF
Smiles CC1CN(CC(O1)C)CC(=O)NC2=CC3=C(C=C2)SC4=C(C3)C=CC=C4C5=CC(=O)C=C(O5)N6CCOCC6
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (182.59 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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In vivo Formulation Calculator

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
what vehicle do you recommend for in vivo use of this compound?

Answer:
The formula for i.p. injections: 5% stock solution (100mg/ml) +30% PEG 300+ddH2O could reach a final concentration of 5mg/ml.

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