product name KU-0060648
Description: KU-0060648 is a dual inhibitor of DNA-PK and PI-3K. KU-0060648 inhibited cellular DNA-PK autophosphorylation with IC(50) values of 0.019 μmol/L (MCF7 cells) and 0.17 μmol/L (SW620 cells), and PI-3K-mediated AKT phosphorylation with IC(50) values of 0.039 μmol/L (MCF7 cells) and more than 10 μmol/L (SW620 cells). KU-0060648 inhibits hepatocellular carcinoma cells through DNA-PKcs-dependent and DNA-PKcs-independent mechanisms.
References: Mol Cancer Ther. 2012 Aug;11(8):1789-98.
582.71
Formula
C33H34N4O4S
CAS No.
881375-00-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 0.4 mg/mL (0.68 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% propylene glycol, 5% Tween 80, 65% D5W: 20 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19411127
| 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. Kinase Assay: Cell Assay: |
|---|---|
| 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 | |
| References | Mol Cancer Ther. 2012 Aug;11(8):1789-98. |
