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Dual DNA-PK/PI3K inhibitor KU-0060648 Small Molecule (Tool Compound)

Invented by Dr Laurent Rigoreau at Cancer Research Technology

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: 2 entries

Robert et al. 2015. Genome Med. 7(1):93. PMID: 26307031.

Munck et al. 2012. Mol Cancer Ther. 11(8):1789-98. PMID: 22576130.


Add a reference

References: 2 entries

Robert et al. 2015. Genome Med. 7(1):93. PMID: 26307031.

Munck et al. 2012. Mol Cancer Ther. 11(8):1789-98. PMID: 22576130.


Add a reference

References: 2 entries

Robert et al. 2015. Genome Med. 7(1):93. PMID: 26307031.

Munck et al. 2012. Mol Cancer Ther. 11(8):1789-98. PMID: 22576130.


Add a reference


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