CKD-501, a novel selective PPARγ agonist, shows no carcinogenic potential in ICR mice following oral administration for 104 weeks.

CKD-501 is a peroxisome proliferator-activated receptor gamma (PPAR) agonist that is effective for the treatment of diabetes. However, its carcinogenic potential remains controversial. The current carcinogenicity study was conducted over a period of 104 weeks in ICR mice. Three groups, each consisting of 60 male and 60 female mice, received oral CKD-501 dosages of 0.2, 1.0 or 6.0 mgkg(-1)day(-1). The mortality rates of the male control, 0.2, 1.0 and 6.0 mg kg(-1)day(-1) treated groups were 60%, 68%, 58% and 67%, respectively and 57%, 68% and 67% in the female control, 0.2 and 1.0mgkg(-1)day(-1) treated groups. It was 67% in the female 6.0mgkg(-1)day(-1) treated group, which was terminated at week 98 due to its increased mortality rate. No significant treatment-related effects were observed on the survival rates, with the exception of females in the 6.0mgkg(-1)day(-1) group. Body weights increased in females receiving 1.0 and 6.0mgkg(-1)day(-1) due to the class effects of the PPAR agonist. Differences were not found in hematology parameters between the CKD-501-treated groups and their corresponding controls, but the histopathological evidence did not reveal any findings attributed to CKD-501. Treated animals exhibited non-neoplastic findings (adipocyte proliferation, bone marrow hypoplasia cardiomyopathy), but all of these were expected changes for this class of compound. There were no treatment-related neoplastic changes in this study. The results of this study therefore demonstrate a lack of carcinogenicity following oral administration of CKD-501 to ICR mice for 104weeks. Copyright (c) 2013 John Wiley & Sons, Ltd. CKD-501 is a peroxisome proliferator-activated receptor gamma (PPAR) agonist that is effective for diabetes. Carcinogenicity study was conducted over a period of 104 weeks in ICR mice with three groups, each consisting of 60 mice in both sexes, received oral dosages of 0.2, 1.0 or 6.0 mg/kg/day. No significant treatment-related effects were observed on the survival rates. Expected non-neoplastic findings for this class of compound (adipocyte proliferation, bone marrow hypoplasia cardiomyopathy) were seen. No treatment-related neoplastic changes were observed.