Home DNA Damage/DNA Repair ATM/ATR inhibitor - Autophagy inhibitor - ULK inhibitor KU-55933 For research use only.

KU-55933

Synonyms: ATM Kinase Inhibitor

KU-55933 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. KU‑55933 (ATM Kinase Inhibitor) inhibits the activation of autophagy‑initiating kinase ULK1 and results in a significant decrease of autophagy.

KU-55933 Chemical Structure

KU-55933 Chemical Structure

CAS: 587871-26-9

Selleck's KU-55933 has been cited by 352 publications

Purity & Quality Control

Batch: Purity: 99.95%
99.95

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Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
DU-145 Growth Inhibition Assay IC50=3.27352 μM SANGER
HuO-3N1 Growth Inhibition Assay IC50=4.17142 μM SANGER
LAMA-84 Growth Inhibition Assay IC50=4.58465 μM SANGER
CAL-72 Growth Inhibition Assay IC50=5.48084 μM SANGER
LoVo Growth Inhibition Assay IC50=6.93239 μM SANGER
HH Growth Inhibition Assay IC50=8.27671 μM SANGER
SK-MEL-3 Growth Inhibition Assay IC50=8.28575 μM SANGER
KM12 Growth Inhibition Assay IC50=9.21142 μM SANGER
NCI-H1437 Growth Inhibition Assay IC50=9.8097 μM SANGER
NCI-H1838 Growth Inhibition Assay IC50=11.1865 μM SANGER
J-RT3-T3-5 Growth Inhibition Assay IC50=11.2417 μM SANGER
GOTO Growth Inhibition Assay IC50=11.6996 μM SANGER
LB2241-RCC Growth Inhibition Assay IC50=11.7186 μM SANGER
ES7 Growth Inhibition Assay IC50=11.788 μM SANGER
KP-N-YS Growth Inhibition Assay IC50=12.6354 μM SANGER
CAL-12T Growth Inhibition Assay IC50=13.617 μM SANGER
COLO-684 Growth Inhibition Assay IC50=14.1569 μM SANGER
DOK Growth Inhibition Assay IC50=15.3329 μM SANGER
Hs-578-T Growth Inhibition Assay IC50=15.4182 μM SANGER
D-423MG Growth Inhibition Assay IC50=15.5236 μM SANGER
DBTRG-05MG Growth Inhibition Assay IC50=15.6111 μM SANGER
VM-CUB-1 Growth Inhibition Assay IC50=15.9849 μM SANGER
KG-1 Growth Inhibition Assay IC50=16.0996 μM SANGER
8305C Growth Inhibition Assay IC50=16.1889 μM SANGER
HuH-7 Growth Inhibition Assay IC50=16.2674 μM SANGER
LXF-289 Growth Inhibition Assay IC50=16.2747 μM SANGER
NCI-H1793 Growth Inhibition Assay IC50=16.4712 μM SANGER
ChaGo-K-1 Growth Inhibition Assay IC50=16.6568 μM SANGER
GCIY Growth Inhibition Assay IC50=16.7905 μM SANGER
SK-MEL-28 Growth Inhibition Assay IC50=17.0475 μM SANGER
NCI-SNU-1 Growth Inhibition Assay IC50=17.1269 μM SANGER
CTB-1 Growth Inhibition Assay IC50=17.2259 μM SANGER
NCI-H82 Growth Inhibition Assay IC50=17.4573 μM SANGER
HCC2998 Growth Inhibition Assay IC50=17.6733 μM SANGER
NCI-H2030 Growth Inhibition Assay IC50=18.1997 μM SANGER
HuP-T3 Growth Inhibition Assay IC50=18.5888 μM SANGER
697 Growth Inhibition Assay IC50=19.0201 μM SANGER
MLMA Growth Inhibition Assay IC50=19.0557 μM SANGER
HCC70 Growth Inhibition Assay IC50=19.489 μM SANGER
A704 Growth Inhibition Assay IC50=19.8305 μM SANGER
D-283MED Growth Inhibition Assay IC50=20.5339 μM SANGER
U031 Growth Inhibition Assay IC50=21.1489 μM SANGER
HSC-3 Growth Inhibition Assay IC50=21.1835 μM SANGER
JVM-3 Growth Inhibition Assay IC50=22.506 μM SANGER
Mewo Growth Inhibition Assay IC50=22.5073 μM SANGER
YH-13 Growth Inhibition Assay IC50=22.5123 μM SANGER
LB1047-RCC Growth Inhibition Assay IC50=22.5879 μM SANGER
HCC2157 Growth Inhibition Assay IC50=22.8054 μM SANGER
SNU-449 Growth Inhibition Assay IC50=22.8748 μM SANGER
Ramos-2G6-4C10 Growth Inhibition Assay IC50=22.96 μM SANGER
CHL-1 Growth Inhibition Assay IC50=23.7292 μM SANGER
SK-MEL-30 Growth Inhibition Assay IC50=24.4662 μM SANGER
PANC-08-13 Growth Inhibition Assay IC50=25.0938 μM SANGER
QIMR-WIL Growth Inhibition Assay IC50=25.1858 μM SANGER
BFTC-905 Growth Inhibition Assay IC50=25.5944 μM SANGER
GI-1 Growth Inhibition Assay IC50=25.7055 μM SANGER
MDA-MB-415 Growth Inhibition Assay IC50=26.5033 μM SANGER
GT3TKB Growth Inhibition Assay IC50=26.5342 μM SANGER
DEL Growth Inhibition Assay IC50=26.8356 μM SANGER
KOSC-2 Growth Inhibition Assay IC50=26.9075 μM SANGER
RVH-421 Growth Inhibition Assay IC50=27.2921 μM SANGER
EW-13 Growth Inhibition Assay IC50=27.4308 μM SANGER
639-V Growth Inhibition Assay IC50=27.5119 μM SANGER
A2780 Growth Inhibition Assay IC50=27.641 μM SANGER
SW982 Growth Inhibition Assay IC50=27.9052 μM SANGER
SW1710 Growth Inhibition Assay IC50=28.0981 μM SANGER
HCC1569 Growth Inhibition Assay IC50=28.4897 μM SANGER
MV-4-11 Growth Inhibition Assay IC50=28.5735 μM SANGER
BHT-101 Growth Inhibition Assay IC50=28.6572 μM SANGER
Ca9-22 Growth Inhibition Assay IC50=28.714 μM SANGER
HAL-01 Growth Inhibition Assay IC50=28.7615 μM SANGER
D-263MG Growth Inhibition Assay IC50=29.344 μM SANGER
NEC8 Growth Inhibition Assay IC50=29.5548 μM SANGER
EKVX Growth Inhibition Assay IC50=31.5847 μM SANGER
EM-2 Growth Inhibition Assay IC50=31.6304 μM SANGER
MFM-223 Growth Inhibition Assay IC50=31.8098 μM SANGER
SK-PN-DW Growth Inhibition Assay IC50=32.1406 μM SANGER
HuO9 Growth Inhibition Assay IC50=32.5282 μM SANGER
MHH-PREB-1 Growth Inhibition Assay IC50=32.6234 μM SANGER
OVCAR-4 Growth Inhibition Assay IC50=32.8363 μM SANGER
NCI-H1648 Growth Inhibition Assay IC50=32.8651 μM SANGER
MKN1 Growth Inhibition Assay IC50=34.1101 μM SANGER
KYSE-450 Growth Inhibition Assay IC50=34.6444 μM SANGER
ES8 Growth Inhibition Assay IC50=34.8975 μM SANGER
MS-1 Growth Inhibition Assay IC50=34.9554 μM SANGER
HOP-92 Growth Inhibition Assay IC50=35.9277 μM SANGER
SKG-IIIa Growth Inhibition Assay IC50=36.2561 μM SANGER
TE-11 Growth Inhibition Assay IC50=36.5243 μM SANGER
SK-NEP-1 Growth Inhibition Assay IC50=37.6744 μM SANGER
DB Growth Inhibition Assay IC50=37.9185 μM SANGER
IA-LM Growth Inhibition Assay IC50=38.0239 μM SANGER
COLO-829 Growth Inhibition Assay IC50=38.4159 μM SANGER
TGBC11TKB Growth Inhibition Assay IC50=39.1408 μM SANGER
CAL-51 Growth Inhibition Assay IC50=40.0612 μM SANGER
NCI-H2228 Growth Inhibition Assay IC50=40.3662 μM SANGER
C32 Growth Inhibition Assay IC50=40.4024 μM SANGER
KU-19-19 Growth Inhibition Assay IC50=40.7683 μM SANGER
KNS-62 Growth Inhibition Assay IC50=40.8381 μM SANGER
FADU Growth Inhibition Assay IC50=41.2502 μM SANGER
CAL-33 Growth Inhibition Assay IC50=42.6749 μM SANGER
CHP-134 Growth Inhibition Assay IC50=42.8496 μM SANGER
HDLM-2 Growth Inhibition Assay IC50=42.9084 μM SANGER
NBsusSR Growth Inhibition Assay IC50=43.0725 μM SANGER
SW954 Growth Inhibition Assay IC50=43.1053 μM SANGER
HCC1806 Growth Inhibition Assay IC50=43.411 μM SANGER
VMRC-RCZ Growth Inhibition Assay IC50=43.4586 μM SANGER
A549 Growth Inhibition Assay IC50=43.931 μM SANGER
NKM-1 Growth Inhibition Assay IC50=43.9558 μM SANGER
DMS-273 Growth Inhibition Assay IC50=44.7567 μM SANGER
TYK-nu Growth Inhibition Assay IC50=45.1234 μM SANGER
KALS-1 Growth Inhibition Assay IC50=45.146 μM SANGER
A101D Growth Inhibition Assay IC50=45.4456 μM SANGER
G-361 Growth Inhibition Assay IC50=46.2138 μM SANGER
KARPAS-299 Growth Inhibition Assay IC50=46.3516 μM SANGER
RS4-11 Growth Inhibition Assay IC50=46.542 μM SANGER
HT-1376 Growth Inhibition Assay IC50=46.7426 μM SANGER
SK-N-AS Growth Inhibition Assay IC50=46.7822 μM SANGER
MG-63 Growth Inhibition Assay IC50=46.9036 μM SANGER
EPLC-272H Growth Inhibition Assay IC50=46.9503 μM SANGER
BALL-1 Growth Inhibition Assay IC50=47.832 μM SANGER
LCLC-97TM1 Growth Inhibition Assay IC50=48.202 μM SANGER
HO-1-N-1 Growth Inhibition Assay IC50=48.9676 μM SANGER
MFE-280 Growth Inhibition Assay IC50=49.4617 μM SANGER
NCI-H526 Growth Inhibition Assay IC50=49.8163 μM SANGER
D-566MG Growth Inhibition Assay IC50=49.9096 μM SANGER
BB30-HNC Growth Inhibition Assay IC50=49.9498 μM SANGER
SK-N-DZ Growth Inhibition Assay IC50=50.0481 μM SANGER
HepG2  Growth Inhibition Assay 10 μM 24 h blocks SC-III3-induced S phase arrest 25527123
HepG2  Function Assay 10 μM 24 h suppresses the phosphorylations of ATM on Ser1981, Chk1 on Ser345, Chk2 on Thr68, and Cdk2 on Tyr15 induced by SC-III3 25527123
KATO III  Growth Inhibition Assay 2.5/5/7.5 μM DMSO enhances the toxicity of olaparib 24841718
hTCEpi Growth Inhibition Assay 10 μM DMSO prevents the cytopathic effect of HSV-1 24370835
MCF10A Growth Inhibition Assay 10 μM 24 h DMSO potentiates the cytotoxicity of GA 24150595
HL-60  Function Assay 10 μM 0.5 h DMSO reduces phosphorylation of Chk2  23934411
MCF-7 Growth Inhibition Assay 1-100μM 24 h FBS inhibits the cell proliferation 23185347
HeLa  Growth Inhibition Assay 1-100μM 24 h FBS inhibits the cell proliferation 23185347
SH-SY5Y Function Assay 10 μM  24 h inhibits clioquinol-induced phosphorylation of p53 22627294
IMR-32 Function Assay 10 μM  24 h inhibits clioquinol-induced phosphorylation of p53 22627294
A549 Function Assay 10 μM  1 h suppresses Nano-Co-induced p53 accumulation 22559321
T47D  Function Assay 20 mM 24 h DMSO prevents IR-induced degradation of IκBα 21144805
A29 MEF Function Assay 10 μM  1h blocks the phosphorylation of Akt at Ser473  20053781
MDA-MB-453  Growth Inhibition Assay 5-40 μM 72 h IC50 of 10 μM 20053781
PC-3 Growth Inhibition Assay 5-40 μM 72 h IC50 of 10 μM 20053781
U2OS Function assay Inhibition of ATM in human U2OS cells assessed as inhibition of p53 phosphorylation at Ser15 residue, IC50 = 0.25 μM. 26632965
MCF7 Function assay 1 hr Inhibition of ATM kinase in human MCF7 cells after 1 hr by immunofluorescence assay, IC50 = 0.3 μM. 26632965
BJ Function assay 10 uM 10 days Suppression of senescence in human BJ cells assessed as increase in cell number at 10 uM after 10 days by senescence reversal assay 16767085
BJ Function assay 10 uM 10 days Inhibition of ataxia telangiectasia-mutated in human BJ cells assessed as increase in cell number at 10 uM after 10 days by senescence reversal assay 16767085
MCF7 Function assay 10 uM 10 mins Sensitization of infrared-induced DNA damage in human MCF7 cells assessed as reduction in colony formation at 10 uM pretreated for 10 mins followed by irradiation for 4 hrs measured after 10 days by crystal violet staining analysis 26632965
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
Click to View More Cell Line Experimental Data

Biological Activity

Description KU-55933 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. KU‑55933 (ATM Kinase Inhibitor) inhibits the activation of autophagy‑initiating kinase ULK1 and results in a significant decrease of autophagy.
Targets
ATM [1]
(Cell-free assay)
12.9 nM
In vitro
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]
Kinase Assay 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 Research 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-AKT(Ser473) / p-AKT(Thr308) PARP / Cleaved PARP / Caspase-3 / Cleaved caspase-3 ATM-S1981 / ATM / p-p53(S15) / p53 p21 / p27 / p53 22739265
Immunofluorescence p-S824 KAP1 / ZEBRA 28249048
In Vivo
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]
Animal Research Animal Models BALB/c nu/nu nude mice bearing LU1205 cells
Dosages 10 μM
Administration --

Chemical lnformation & Solubility

Molecular Weight 395.49 Formula

C21H17NO3S2
CAS No. 587871-26-9 SDF Download KU-55933 SDF
Smiles C1COCCN1C2=CC(=O)C=C(O2)C3=C4C(=CC=C3)SC5=CC=CC=C5S4
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 39 mg/mL ( (98.61 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

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