Dual DNA-PK/PI3K inhibitor KU-0060648 Small Molecule (Tool Compound)
Invented by Dr Laurent Rigoreau from Cancer Research Horizons
Invented at University of Newcastle upon Tyne
- Datasheet
- References (4)
- Inventor Info
Info
| Catalogue Number | 152709 |
| Antigen/Gene or Protein Targets | Dual PI 3-K and DNA-PK inhibitor |
| Type | Inhibitor |
| Relevance | KU-0060648 is a dual PI3-K and DNA-PK inhibitor (IC50 values are <0.1, 0.5, 4 and 19 nM for PI 3-Kδ, PI 3-Kβ, PI 3-Kα and DNA-PK respectively). It inhibits proliferation of MCF7 cells in vitro and delays growth of MCF7 xenografts in mice. KU-0060648 can also enhance CRISP-Cas9-mediated homology-directed repair (HDR) efficiency, and attenuate nonhomologous end-joining (NHEJ). |
| On Target IC50 | 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. |
| Molecular Formula | C33H34N4O4S |
| Molecular Weight (g/mol) | 582.71 |
| In vivo applications | 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. |
| In vitro applications | 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 |
| Solubility | Soluble to 100 mM in 2eq.HCl |
| Research Area | Cell Signaling & Signal Transduction, DNA Damage and Repair, Epigenetics & Nuclear Signalling |
| Storage | Store at -20°C |
References: 4 entries
Robert et al. 2015. Genome Med. 7(1):93. PMID: 26307031.
Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing.
Europe PMC ID: 26307031
Munck et al. 2012. Mol Cancer Ther. 11(8):1789-98. PMID: 22576130.
Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K.
Europe PMC ID: 22576130
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References: 4 entries
Robert et al. 2015. Genome Med. 7(1):93. PMID: 26307031.
Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing.
Munck et al. 2012. Mol Cancer Ther. 11(8):1789-98. PMID: 22576130.
Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K.
Add a reference
