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Chemical Structure| 925701-46-8 Chemical Structure| 925701-46-8

Structure of KU-60019
CAS No.: 925701-46-8

Chemical Structure| 925701-46-8

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KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM.

4.5 *For Research Use Only !

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Product Details of KU-60019

CAS No. :925701-46-8
Formula : C30H33N3O5S
M.W : 547.67
SMILES Code : O=C(NC1=CC(CC2=C(C(C3=CC(C=C(N4CCOCC4)O3)=O)=CC=C2)S5)=C5C=C1)CN6C[C@@H](C)O[C@@H](C)C6
MDL No. :MFCD18384974
InChI Key :SCELLOWTHJGVIC-BGYRXZFFSA-N
Pubchem ID :15953870

Safety of KU-60019

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of KU-60019

DNA
PI3K-AKT

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
human osteosarcoma cells (U2OS) 2 µM 72 hours increase 1-bp insertion frequency Nat Commun. 2021 Aug 25;12(1):5111
mouse embryonic stem cells (mESC) 2 µM 72 hours increase 1-bp insertion frequency Nat Commun. 2021 Aug 25;12(1):5111
C4–2 cells 2 μM 72 hours KU-60019 in combination with Enzalutamide re-sensitized C4–2/N-Myc cells to Enzalutamide. Mol Cancer. 2019 Jan 18;18(1):11
human diploid fibroblasts (HDFs) 0.5 μM 15 days Co-inhibition of ATM and ROCK by KU-60019 and Y-27632 synergistically increases the proliferation of HDFs undergoing replicative senescence through activation of transcription factors E2F1 and FOXM1 Commun Biol. 2022 Jul 14;5(1):702
HEK293FT cells 1 μM 48 hours Inhibition of ATM activity, leading to accumulation of cytoplasmic DNA. J Neurosci. 2019 Aug 7;39(32):6378-6394
LNCaP cells 10 μM KU-60019 significantly reduced the percentage of ADT-induced SA-β-gal positive senescent cells, indicating the involvement of ATM in ADT-induced senescence. Mol Cancer. 2019 Jan 18;18(1):11
RKOΔHDAC2 cells 0.5-3 µM 48 hours KU-60019 inhibits ATM kinase, sensitizing RKOΔHDAC2 cells to cytotoxic effects of 5-FU, inducing cell cycle arrest and apoptosis. Cell Biol Toxicol. 2023 Oct;39(5):2401-2419
RKO cells 0.5-3 µM 48 hours KU-60019 inhibits ATM kinase, sensitizing RKO cells to cytotoxic effects of 5-FU, inducing cell cycle arrest and apoptosis. Cell Biol Toxicol. 2023 Oct;39(5):2401-2419
WT cortical neurons 1 µM 24 hours Inhibition of ATM kinase activity, leading to increased SQSTM1 puncta Autophagy. 2021 Aug;17(8):1998-2010
HT22 cells 1 µM 24 hours Inhibition of ATM kinase activity, leading to increased ATM protein levels Autophagy. 2021 Aug;17(8):1998-2010
MC38 1 μM 24 hours Enhanced radiosensitivity through H2O2-dependent oxidative damage and increased DNA damage Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):933-944
CT26 1 μM 24 hours Enhanced radiosensitivity through H2O2-dependent oxidative damage and increased DNA damage Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):933-944
HT29 1 μM 24 hours Enhanced radiosensitivity through H2O2-dependent oxidative damage and increased DNA damage Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):933-944
SW480 1 μM 24 hours Enhanced radiosensitivity through H2O2-dependent oxidative damage and increased DNA damage Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):933-944
HCT116 1 μM 24 hours Enhanced radiosensitivity through H2O2-dependent oxidative damage and increased DNA damage Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):933-944
Peripheral blood mononuclear cells (PBMCs) 3 µM 1 hour To investigate the inhibitory effect of KU-60019 on ATM activation and validate its suppression of p53 downstream targets. Results showed that KU-60019 inhibited radiation-induced p53 accumulation, thereby preventing the upregulation of miR-34a-5p in PBMCs and EVs. Cell Commun Signal. 2024 Oct 2;22(1):471
KP6 and KPP4 0.3 µM and 3 µM 3 hours pre-treatment Restored radiation sensitivity in PTEN-deficient cells Cell Biosci. 2022 Apr 27;12(1):50
BEAS-2B PTENhomo 0.3 µM and 3 µM 3 hours pre-treatment Restored radiation sensitivity in PTEN-deficient cells Cell Biosci. 2022 Apr 27;12(1):50
PBLCs 3 µM 24 hours Inhibition of ATM significantly protected unstimulated PBLCs from radiation-induced cell death Cell Death Dis. 2018 Oct 15;9(11):1053
microglia 1 μM 48 hours Inhibition of ATM kinase activity, leading to microglial activation and morphological changes, and increased production of pro-inflammatory cytokines. J Neurosci. 2019 Aug 7;39(32):6378-6394

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice HCT116 and MC38 tumor models Tail vein injection 0.5 mg/kg 3 hours before radiation Enhanced tumor radiosensitivity while reducing intestinal toxicity Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):933-944
Mice KP6 and KPP4 cell transplantation model In vitro culture 3 µM 8 days observation KU-60019 combined with radiation led to regression of PTEN-deficient tumors Cell Biosci. 2022 Apr 27;12(1):50

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.83mL

0.37mL

0.18mL

9.13mL

1.83mL

0.91mL

18.26mL

3.65mL

1.83mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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