KU-55933 (ATM Kinase Inhibitor)

Catalog No.S1092

KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor with IC50/Ki of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.

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KU-55933 (ATM Kinase Inhibitor) Chemical Structure

KU-55933 (ATM Kinase Inhibitor) Chemical Structure
Molecular Weight: 395.49

Validation & Quality Control

Cited by 35 publications:

4 customer reviews :

Quality Control & MSDS

Related Compound Libraries

KU-55933 (ATM Kinase Inhibitor) is available in the following compound libraries:

ATM/ATR Inhibitors with Unique Features

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    CGK 733 Dual ATM/ATR inhibitor, IC50=~200 nM.

  • Most Potent ATM/ATR Inhibitor

    AZ20 ATR, IC50=5 nM.

  • ATM/ATR Inhibitor in Clinical Trial

    BEZ235 (NVP-BEZ235, Dactolisib) Phase II for Advanced Endometrial Carcinoma.

  • Newest ATM/ATR Inhibitor

    VE-822 ATR inhibitor with IC50 of 19 nM.

Product Information

  • Compare ATM/ATR Inhibitors
    Compare ATM/ATR Products
  • Research Area
  • Inhibition Profile

Product Description

Biological Activity

Description KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor with IC50/Ki of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.
Targets ATM [1]
(Cell-free assay)
DNA-PK [1]
(Cell-free assay)
mTOR [1]
(Cell-free assay)
PI3K [1]
(Cell-free assay)

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IC50 12.9 nM 2.5 μM 9.3 μM 16.6 μM
In vitro KU-55933 inhibits DNA-PK and PI3K with IC50 of 2.5 μM and 16.6 μM, respectively. Besides, KU-55933 also prevents the activity of mTOR with IC50 of 9.3 μM. KU-55933 is active at the cellular level in ablating a well-characterized ATM-dependent phosphorylation event. KU-55933 has a dose-dependent effect in inhibiting this ATM-dependent phosphorylation event with IC50 of 300 nM. KU-58050 does not prevent the ATM-dependent phosphorylation of p53 serine 15 until a dose of 30 μM. Addition of KU-55933 has no appreciable effects on UV-induced phosphorylation of H2AX on serine 139, NBS1 on serine 343, CHK1 on serine 345, and SMC1 on serine 966. In stark contrast to the UV responses, KU-55933 ablates the ionizing radiation-induced phosphorylation of these ATM substrates. KU-55933 sensitizes HeLa cells to a range of ionizing radiation doses. [1] KU-55933 inhibits the phosphorylation of Akt induced by growth factors in cancer cells. KU-55933 suppresses the proliferation of cancer cells. Furthermore, suppression of ATM by KU-55933 improves survival, probably via prevention of downstream activation of TAp63α. [2]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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LAMA-84Mk\pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MWDJR|UxRTRwNUi0OlUh|ryPMki4V2FPT0WU
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G-361MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MXHJR|UxRTR4LkKxN|gh|ryPNX3sUo5SW0GQR1XS
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RS4-11NHHINWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4nBS2lEPTB;NE[uOVQzKM7:TR?=Ml7EV2FPT0WU
HT-1376MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1O5WGlEPTB;NE[uO|QzPiEQvF2=NIrtR4JUSU6JRWK=
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MG-63MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MXfJR|UxRTR4LkmwN|Yh|ryPMX;TRW5ITVJ?
EPLC-272HNIXRXoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NGPIepFKSzVyPUS2Mlk2ODNizszNNULDe3ZVW0GQR1XS
BALL-1NWTrTWlbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MmT5TWM2OD12Nz64N|Ih|ryPM1XYO3NCVkeHUh?=
LCLC-97TM1NIrvfndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoLyTWM2OD12OD6yNFIh|ryPNGrJe5pUSU6JRWK=
HO-1-N-1Ml\uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYDMO2ZVUUN3ME20PE46Pjd4IN88US=>M1XKfXNCVkeHUh?=
MFE-280MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3rWb2lEPTB;NEmuOFYyPyEQvF2=NHi4UpdUSU6JRWK=
NCI-H526MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NIDscZRKSzVyPUS5MlgyPjNizszNM{nMZnNCVkeHUh?=
D-566MGMYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NU\KU25XUUN3ME20PU46ODl4IN88US=>MYLTRW5ITVJ?
BB30-HNCNHy5c4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MkPvTWM2OD12OT65OFk5KM7:TR?=NHG3cVhUSU6JRWK=
SK-N-DZNWXsN5dyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M4fD[GlEPTB;NUCuNFQ5OSEQvF2=MojEV2FPT0WU
HepG2 NV\nU5NsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M4LCb|ExyqEQvF2=M1LTWVI1KGh?NHvpbJBjdG:la4OgV2MuUUmLMz3pcoR2[2WmIGOgdIhie2ViYYLy[ZN1Mn;ENlU2OjdzMkO=
HepG2 NIKwOopHfW6ldHnvckBCe3OjeR?=NX[zN|YyOTEEoN88US=>MmGxNlQhcA>?NETqeHd{fXCycnXzd4V{KHSqZTDwbI9{eGixconsZZRqd26|IH;mJGFVVSCxbjDT[ZIyQThzLDDDbIsyKG:wIGPldlM1PSxiQ3jrNkBwdiCWaIK2PEwh[W6mIFPkb|Ihd25iVInyNVUhcW6mdXPl[EBjgSCVQz3JTWk{MmrhNlU2OjdzMkO=
KATO III MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MXyyMlUwPS95LkWg{txONULMNXRZTE2VTx?=MU\lcohidmOnczD0bIUhfG:6aXPpeJkhd2Zib3zhdIFzcWJ?M3H0Z|I1QDRzN{G4
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MCF10AMkPmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYLMSYFTOTBizszNNWnZcGI4OjRiaB?=MX;EUXNQNV22[VY4eG:2ZX70bYF1\XNidHjlJIN6fG:2b4jpZ4l1gSCxZjDHRS=>NXXVWlBqOjRzNUC1PVU>
HL-60 Mn7WSpVv[3Srb36gRZN{[Xl?MlvkNVAh|ryPM3vid|AvPSCqM{Xqc2ROW09?MmLLdoVlfWOnczDwbI9{eGixconsZZRqd25ib3[gR4hsOsLiNW\vd5lqOjN7M{S0NVE>
MCF-7M33pfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NH;aOmkyNTFyMN88US=>MXSyOEBpM3XUU2ZDWw>?NGTRUVFqdmirYnn0d{B1cGViY3XscEBxem:uaX\ldoF1cW:wMVKyN|E5PTN2Nx?=
HeLa NYTIWG9YT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NG[x[VQyNTFyMN88US=>MVyyOEBpNXO1Z4o3TkKVMUPpcohq[mm2czD0bIUh[2WubDDwdo9tcW[ncnH0bY9vM4nKXlI{OTh3M{S3
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IMR-32MkLBSpVv[3Srb36gRZN{[Xl?MlHwNVDDqM7:TdMgM3;KV|I1KGh?M3Ph[YlvcGmkaYTzJINtcW:zdXnuc4wucW6mdXPl[EBxcG:|cHjvdplt[XSrb36gc4YheDV|M2rac|IzPjJ5Mkm0
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T47D NHnaV5pHfW6ldHnvckBCe3OjeR?=NVu0WHZ5OjEEoH3NNVnEXFF{OjRiaB?=NHLLOmFFVVORM3z6UJBz\X[nboTzJGlTNWmwZIXj[YQh\GWpcnHkZZRqd25ib3[gTe67Ss7zMlWxNlEyPDR6MEW=
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MDA-MB-453 NYPCWVNzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYXaWGNuPS12MDFOwG0>NVPwU5J4PzJiaB?=MXHJR|UxKG:oIEGwJO69VQ>?NU\ud3FXOjByNUO3PFE>
PC-3MoLTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MX[1MVQxKM7:TR?=NIHP[3g4OiCqNFPVZm9KSzVyIH;mJFExKM7:TR?=MVeyNFA2Ozd6MR?=

... Click to View More Cell Line Experimental Data

In vivo Suppression of ATM-dependent STAT3 activation by KU-55933 enhances TRAIL-mediated apoptosis through up-regulation of surface DR5 expression, whereas suppression of both STAT3 and NF-κB appeares to be involved in down-regulation of cFLIP accompanied by an additional increase in apoptotic levels. The ATM inhibitor KU-55933 affectes TRAIL-mediated apoptosis more strongly than the JAK2 inhibitor, AG490, or overexpression of STAT3β. [3]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

Purified enzyme assays ATM for use in the in vitro assay is obtained from HeLa nuclear extract by immunoprecipitation with rabbit polyclonal antiserum raised to the COOH-terminal 400 amino acids of ATM in buffer containing 25 mM HEPES (pH 7.4), 2 mM MgCl2, 250 mM KCl, 500 μM EDTA, 100 μM Na3VO4, 10% v/v glycerol, and 0.1% v/v Igepal. ATM-antibody complexes are isolated from nuclear extract by incubating with protein A-Sepharose beads for 1 hour and then through centrifugation to recover the beads. In the well of a 96-well plate, ATM-containing Sepharose beads are incubated with 1 μg of substrate glutathione S-transferase–p53N66 (NH2-terminal 66 amino acids of p53 fused to glutathione S-transferase) in ATM assay buffer [25 mM HEPES (pH 7.4), 75 mM NaCl, 3 mM MgCl2, 2 mM MnCl2, 50 μM Na3VO4, 500 μM DTT, and 5% v/v glycerol] at 37 °C in the presence or absence of inhibitor. After 10 minutes with gentle shaking, ATP is added to a final concentration of 50 μM and the reaction continued at 37 °C for an additional 1 hour. The plate is centrifuged at 250 × g for 10 minutes (4 °C) to remove the ATM-containing beads, and the supernatant is removed and transferred to a white opaque 96-well plate and incubated at room temperature for 1.5 hours to allow glutathione S-transferase-p53N66 binding. This plate is then washed with PBS, blotted dry, and analyzed by a standard ELISA technique with a phospho-serine 15 p53 antibody. The detection of phosphorylated glutathione S-transferase-p53N66 substrate is performed in combination with a goat antimouse horseradish peroxidase-conjugated secondary antibody. Enhanced chemiluminescence solution is used to produce a signal and chemiluminescent detection is carried out.

Cell Assay: [1]

Cell lines U2OS cells
Concentrations 10 μM
Incubation Time 2 hours
Method U2OS cells are exposed to ionizing radiation (3, 5, or 15 Gy) or UV (5 or 50 J/m2) and the ATM response determined by Western blot analysis of p53 serine 15 phosphorylation and stabilization of wild-type p53. Whole cell extracts are obtained from each time point, proteins separated by SDS-PAGE, and the ATM-specific increase in phosphorylated serine 15 measured with a p53 phospho-serine 15 specific antibody. Overall p53 stabilization with time is also observed with a p53-specific antibody (DO-1). Similarly, for studying ATM-dependent phosphorylations on H2AX, CHK1, NBS1, and SMC1, the following antibodies are used: CHK1 phospho-serine 345 and NBS1 phospho-serine 343 antibodies. Histone H2A (H-124) and CHK1 antibodies are also used, as well as SMC1 and SMC1 phospho-serine 966 antibodies. For determination of a cellular IC50 for KU-55933, the peak response time for p53 serine 15 phosphorylation of 2 hours is used to monitor inhibition of ATM. KU-55933 is titrated onto cells and preincubated for 1 hour before ionizing radiation. Using scanning densitometry, the percentage inhibition relative to vehicle control is calculated, and the IC50 value is calculated as for the in vitro determinations.

Animal Study: [3]

Animal Models BALB/c nu/nu nude mice bearing LU1205 cells
Formulation
Dosages 10 μM
Administration

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Hickson I, et al. Cancer Res. 2004, 64(24), 9152-9159.

[2] Soleimani R, et al. Aging. 2011, 3(8), 782-793.

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Chemical Information

Download KU-55933 (ATM Kinase Inhibitor) SDF
Molecular Weight (MW) 395.49
Formula

C21H17NO3S2

CAS No. 587871-26-9
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 33 mg/mL (83.44 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 5% DMSO and 47.5% PEG300 10 mg/mL
* <1 mg/ml means slightly soluble or 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 Name 2-morpholino-6-(thianthren-1-yl)-4H-pyran-4-one

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.

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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