KU-60019

Catalog No.S1570

For research use only.

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

CAS No. 925701-49-1

Selleck's KU-60019 has been cited by 106 publications

Purity & Quality Control

Choose Selective ATM/ATR Inhibitors

Other ATM/ATR Products

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

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 Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BAECs NFHtZoJHfW6ldHnvckBCe3OjeR?= MWKxNOKh|ryP Ml6wNeKhcMLi NF7RWlZFVVOR MlTOZYJwdGm|aHXzJJRp\SCyaH;zdIhwenmuYYTpc44hd2ZiQWTNMXNmejF7OEG= MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTR7OEW0Nkc,OjV2OUi1OFI9N2F-
BAECs NF25NXpHfW6ldHnvckBCe3OjeR?= MVmxNOKh|ryP NUDZPG9IOcLiaNMg MY\EUXNQ NITHS45qdmirYnn0d{B1cGViaX7jdoVie2ViaX6gUm9UKGGldHn2bZR6 NI\XbpM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUS5PFU1Oid-MkW0PVg2PDJ:L3G+
U1242 M4DaR2tqdmG|ZTDBd5NigQ>? MlnJN{DPxE4EoB?= MlrUNE42KGh? NInqN49FVVOR NIrT[3dqdmirYnn0d{B1cGViQWTNJItqdmG|ZR?= NF[2fXA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[yNFQxQSd-MkO2NlA1ODl:L3G+
U87 M3OzTmtqdmG|ZTDBd5NigQ>? MoPiN{DPxE4EoB?= NHv5[G0xNjViaB?= NFrDUJdFVVOR NX3kUGNEcW6qaXLpeJMhfGinIFHUUUBscW6jc3W= NIGzPGI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[yNFQxQSd-MkO2NlA1ODl:L3G+
U1242 Ml25RZBweHSxc3nzJGF{e2G7 NYXBPWZkOyEQvF5CpC=> M4C5NVHDqGkEoB?= M2j1eWROW09? NI\2cnJz[WSrb4PlcpNqfGm8ZYOgbJVu[W5iZ3zpc41iKGOnbHzz M3rPflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NkKwOFA6Lz5{M{[yNFQxQTxxYU6=
U87 MkDrRZBweHSxc3nzJGF{e2G7 M2rrSlMh|ryPwrC= MWmxxsBpyqB? NWnEfm1WTE2VTx?= M2OyOZJi\Gmxc3Xud4l1cXqnczDoeY1idiCpbHnvcYEh[2WubIO= M{LjNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NkKwOFA6Lz5{M{[yNFQxQTxxYU6=
U1242  NYT6SVhLU2mwYYPlJGF{e2G7 MVewMlAyNTNizszNxsA> M1T5[FEhcA>? NVnSbpV4TE2VTx?= MkTEZoxw[2u|IFHUUUBscW6jc3WgZYN1cX[rdImgZZQhdG:5IHPvcoNmdnS{YYTpc45{ M3vXOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{ewOFg2Lz5{MkO3NFQ5PTxxYU6=
glioma MV3GeY5kfGmxbjDhd5NigQ>? M4HydGlvcGmkaYTpc44hd2ZiQWTNJItqdmG|ZTDpckBpfW2jbjDncIlwdWFiY3XscJMtKEmFNUCgQUAxNjByNjFOwG0v MlPVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV|OEexOVMoRjJ3M{i3NVU{RC:jPh?=
A673 MoLDdWhVWyCjc4PhfS=> MULxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSTZ5MzDj[Yxtew>? NGHCRnM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Saos-2 NWDk[4V2eUiWUzDhd5NigQ>? M1ryPZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVYX;zMVIh[2WubIO= NIX6Nlc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
OHS-50 M1;1bJFJXFNiYYPzZZk> NUTtendOeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=> MmS3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
SJ-GBM2 MX7xTHRUKGG|c3H5 NUjtO5NFeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM> NHL1dJU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
SK-N-MC MoLmdWhVWyCjc4PhfS=> NED6fI1yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1OSyClZXzsdy=> NE[0S3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
NB-EBc1 NWK1WYk4eUiWUzDhd5NigQ>? M1HQNpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQj3FRoMyKGOnbHzz NIrwRmg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
LAN-5 NHjrVllyUFSVIHHzd4F6 MoHHdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEyDTj21JINmdGy| NXTaeGo4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh18 NFX6Z|RyUFSVIHHzd4F6 NX3hUWFEeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGLoNVgh[2WubIO= NFnQV|I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Assay
Methods Test Index PMID
Western blot p-ATM / ATM / p-AKT / AKT / PKM2 30799198
Immunofluorescence GLUT1 30799198
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]

Protocol (from reference)

Cell Research:

[1]

  • 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.

  • (Only for Reference)
Animal Research:

[2]

  • 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
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 18 mg/mL warmed
(32.86 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 547.67
Formula

C30H33N3O5S

CAS No. 925701-49-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1CN(CC(O1)C)CC(=O)NC2=CC3=C(C=C2)SC4=C(C3)C=CC=C4C5=CC(=O)C=C(O5)N6CCOCC6

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

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

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.

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.

Tags: buy KU-60019|KU-60019 ic50|KU-60019 price|KU-60019 cost|KU-60019 solubility dmso|KU-60019 purchase|KU-60019 manufacturer|KU-60019 research buy|KU-60019 order|KU-60019 mouse|KU-60019 chemical structure|KU-60019 mw|KU-60019 molecular weight|KU-60019 datasheet|KU-60019 supplier|KU-60019 in vitro|KU-60019 cell line|KU-60019 concentration|KU-60019 nmr|KU-60019 in vivo|KU-60019 clinical trial|KU-60019 inhibitor|KU-60019 DNA Damage inhibitor