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    KU-0060648 HCL
    KU-0060648 HCL

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0254
    CAS #: N/APurity ≥98%

    Description: KU0060648 HCl is a novel, potent and dual inhibitor of DNA-dependent protein kinase (DNA-PK) and PI3Kα/β/δ  (Phosphoinositide 3-kinases) with potential antitumor activity. It inhibits DNA-PK and PI3Kα/β/δ  with an IC50 of 8.6 nM and 4 nM, 0.5 nM, 0.1 nM respectively. It exhibits 20-1000 fold higher selectivity for DNA-PK over other PIKKs and a panel of 60 other kinases. 

    KU-0060648 showed potent antiproliferative activity in vitro and high antitumor efficacy in vivo.

    References:Mol Cancer Ther. 2012 Aug;11(8):1789-98. 

    Related CAS: 881375-00-4 (free base)

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    Molecular Weight (MW)

    618.21

    Formula

    C33H35ClN4O4S 

    CAS No.

    N/A

    Storage

    -20℃ for 3 years in powder form

    -80℃ for 2 years in solvent

    Solubility (In vitro)

    DMSO: 10 mM

    Water: N/A

    Ethanol: N/A

    Solubility (In vivo)

    30% propylene glycol, 5% Tween 80, 65% D5W: 20 mg/mL

    Synonyms

    KU-0060648 HCl; KU 0060648; KU0060648.


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    In Vitro

    In vitro activity: 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.

    In Vivo

    In mice bearing SW620 and MCF7 xenografts, KU-0060648 concentrations that were sufficient for in vitro growth inhibition and chemosensitization were maintained within the tumor at nontoxic doses for at least 4 hours. KU-0060648 alone delayed the MCF7 xenografts growth and increased etoposide-induced tumor growth delay in both in MCF7 and SW620 xenografts by up to 4.5 folds, without causing etoposide toxicity to unacceptable levels

    Animal model

     Mice bearing SW620 and MCF7 xenografts

    Formulation & Dosage

     N/A

    References

    Mol Cancer Ther. 2012 Aug;11(8):1789-98. 


    These protocols are for reference only. InvivoChem does not independently validate these methods.

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