KU-0060648

Catalog No.S8045 Batch:S804503

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Technical Data

Formula

C33H34N4O4S
Molecular Weight 582.71 CAS No. 881375-00-4
Solubility (25°C)* In vitro DMSO 2 mg/mL (3.43 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description KU-0060648 is a dual inhibitor of DNA-PK and PI3Kα, PI3Kβ, PI3Kδ with IC50 of 8.6 nM and 4 nM, 0.5 nM, 0.1 nM respectively, less inhibition of PI3Kγ with IC50 of 0.59 μM.
Targets
PI3Kδ [1]
(Cell-free assay)		 PI3Kβ [1]
(Cell-free assay)		 PI3Kα [1]
(Cell-free assay)		 DNA-PK [1]
(Cell-free assay)		 PI3Kγ [1]
(Cell-free assay)
0.1 nM 0.5 nM 4 nM 5 nM 0.59 μM
In vitro

KU-0060648 exhibits differential effects on growth inhibition, but is not profoundly cytotoxic in a panel of human cancer cell lines. It inhibits DNA-PK and PI-3K with greater potency in MCF7 than SW620 cell using cell-based assays. Five-day exposure to 1 mM KU-0060648 inhibits cell proliferation by more than 95% in MCF7 cells but only by 55% in SW620 cells. 

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    MCF7, T47D, MDA-MB-231, LoVo and SW620

  • Concentrations

    ~1 μM

  • Incubation Time

    5 day

  • Method

    SRB assay
Animal Study:

[1]
  • Animal Models

    human-tumor SW620 or MCF7 xenograft models

  • Dosages

    10 mg/kg, twice daily

  • Administration

    i.p.

References

  • https://pubmed.ncbi.nlm.nih.gov/22576130/
  • http://mct.aacrjournals.org/cgi/content/meeting_abstract/8/12_MeetingAbstracts/A138

Customer Product Validation

a/ Western blot showing knock down efficiency obtained with the siRNAs targeting either Ku70 or Ku80. b/ Quantitation of genome editing events from cells transfected with pQCiG-TLR and ΔeGFP donor in the presence of 2 μM NU7441, 250 nM KU-0060648, siRNAs targeting Ku70, Ku80, DNA-PKcs or DNA ligase IV, 1 μM Scr7, or a combination of Scr7 and 2 μM NU7441 or 250 nM KU-0060648. The HDR and NHEJ values are relative to those obtained with Cas9, sgRNA, and ΔeGFP donor in the presence of vehicle (DMSO). Results are from biological replicates performed in technical duplicates. Significance (relative to vehicle) was calculated using the Student’s t-test: *p ≤0.05; **p ≤0.01; ns, not significant.

Data from [ , , Genome Med, 2015, 7:93 ]

D, Different mutation efficiencies were induced by transfection of proportional sgHPRT and control plasmid. The data were presented in a three-dimension plot where x-axis showed the temperature, y-axis showed the ΔF, and z-axis showed the mutation efficiency. E, Correlation of the mutation efficiency with the maximum value of ΔF (ΔFmax).

Data from [ , , Mol Cancer Ther, 2018, 17(2): 419-31 ]

Selleck's KU-0060648 Has Been Cited by 11 Publications

Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer [ Breast Cancer Res, 2022, 24(1):41] PubMed: 35715861
Identifying Novel Actionable Targets in Colon Cancer [ Biomedicines, 2021, 9(5)579] PubMed: 34065438
Development of a CRISPR-Cas9 Based Luciferase Turn-On System as Nonhomologous End Joining Pathway Reporter [ Chembiochem, 2021, 22(12):2177-2181] PubMed: 33882189
UBQLN4 Represses Homologous Recombination and Is Overexpressed in Aggressive Tumors [Jachimowicz RD, et al Cell, 2019, 176(3):505-519] PubMed: 30612738
Temozolomide Induces Senescence and Repression of DNA Repair Pathways in Glioblastoma Cells via Activation of ATR-CHK1, p21, and NF-κB [ Cancer Res, 2019, 79(1):99-113] PubMed: 30361254
Curcumin sensitizes lymphoma cells to DNA damage agents through regulating Rad51-dependent homologous recombination [Zhao Q, et al. Biomed Pharmacother, 2018, 97:115-119] PubMed: 29080451
Modeling chemotherapy-induced stress to identify rational combination therapies in the DNA damage response pathway [ Sci Signal, 2018, 11(540)eaat0229] PubMed: 30042127
A CRISPR/Cas9-Based Screening for Non-Homologous End Joining Inhibitors Reveals Ouabain and Penfluridol as Radiosensitizers [Du J, et al. Mol Cancer Ther, 2018, 17(2):419-431] PubMed: 28864683
Targeting Homologous Recombination by Pharmacological Inhibitors Enhances the Killing Response of Glioblastoma Cells Treated with Alkylating Drugs. [ Mol Cancer Ther, 2016, 15(11):2665-2678] PubMed: 27474153
Artesunate enhances the therapeutic response of glioma cells to temozolomide by inhibition of homologous recombination and senescence. [Berte N, et al. Oncotarget, 2016, 7(41):67235-67250] PubMed: 27626497

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.