KU-0060648

Catalog No.S8045 Batch:S804504

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Technical Data

Formula

C33H34N4O4S
Molecular Weight 582.71 CAS No. 881375-00-4
Solubility (25°C)* In vitro DMSO 3 mg/mL (5.14 mM)
Water Insoluble
Ethanol Insoluble
* <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. In clonogenic survival assays, KU-0060648 increases the cytotoxicity of etoposide and doxorubicin across the panel of DNA-PKcs-proficient cells, but not in DNA-PKcs-deficient cells, confirming that enhanced cytotoxicity of the topoisomerase II poisons etoposide and doxorubicin is due to DNA-PK inhibition. [1]
In vivo KU-0060648 enhances the anti-tumour activity of etoposide in both MCF7 and SW620 xenograft models, and has single-agent activity in the MCF7 xenograft model. [1]

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.

Customer Product Validation

Data from [Data independently produced by , , Genome Med, 2015, 7:93]

Data from [Data independently produced by , , 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.

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