Determination of maximum tolerated dose and toxicity of Inauhzin in mice

Abstract

Reactivating the tumor suppressor p53 offers an attractive strategy for developing cancer therapy. We recently identified Inauhzin (INZ) as a novel non-genotoxic p53-activating compound. To develop INZ into a clinically applicable anticancer drug, we have initiated preclinical toxicity studies. Here, we report our study on determining the maximum tolerated dose (MTD) of INZ analog, Inauhzin-C (INZ (C)), following intraperitoneal (i.p.) administration (Phase A) and its toxicity following i.p. administration over a period of 5-day dosing plus 2-day recovery (Phase B) in CD-1 mice. The Phase A study showed that the MTD of INZ (C) is 200 mg/kg for female and 250 mg/kg for male, respectively. The Phase B study showed that the administration of INZ (C) via 5-day consecutive i.p. injection is tolerated by female CD-1 mice at all dose levels tested from 50 mg/kg to 120 mg/kg without significant changes in biochemical and pathological parameters in the animals. Together, these results indicate that our previously determined effective dose of INZ at 30–60 mg/kg via i.p. is quite safe to mice, and imply that this compound have the features worthy for further development into a clinically applicable drug.

Keywords

• Inauhzin
• Mouse
• Toxicity study
• Dose range finding
• Maximum tolerated dose