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J Appl Toxicol. 2014 Dec;34(12):1271-84. doi: 10.1002/jat.2918. Epub 2013 Sep 12.

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

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  • 1Division of Non-clinical Studies, Korea Institute of Toxicology (KIT), Daejeon, Korea; Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chungnam National University, Daejeon, Korea.

Abstract

CKD-501 is a peroxisome proliferator-activated receptor gamma (PPARγ) 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 mg kg(-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 1.0 mg kg(-1)  day(-1) treated groups. It was 67% in the female 6.0 mg kg(-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 6.0 mg kg(-1)  day(-1) group. Body weights increased in females receiving 1.0 and 6.0 mg kg(-1)  day(-1) due to the class effects of the PPARγ 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 104 weeks.

Copyright © 2013 John Wiley & Sons, Ltd.

KEYWORDS:

CKD-501; Carcinogenicity; ICR mice·adipocyte proliferation; PPARγ agonist

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