title: 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 50mg/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.
authors.affiliation: Department of Biochemistry & Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, 1430 Tulane Avenue, Louisiana, LA 70112.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry & Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, 1430 Tulane Avenue, Louisiana, LA 70112.
authors.forename: Shelya X
authors.initials: SX
authors.lastname: Zeng
authors.affiliation: Department of Biochemistry & Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, 1430 Tulane Avenue, Louisiana, LA 70112.
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
keywords: Inauhzin; dose range finding; maximum tolerated dose; mouse; toxicity study