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.

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.