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CKD‐501, a novel selective PPARγ agonist, shows no carcinogenic potential in ICR mice following oral administration for 104 weeks
Author(s) -
Moon KyoungSik,
Lee JiEun,
Lee Hee Su,
Hwang InChang,
Kim DalHyun,
Park HyunKyu,
Choi HyunJi,
Jo Woori,
Son WooChan,
Yun HyoIn
Publication year - 2014
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2918
Subject(s) - agonist , medicine , endocrinology , dose , oral administration , carcinogen , toxicity , receptor , biology , genetics
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.