title: CKD-501, a novel selective PPARγ agonist, shows no carcinogenic potential in ICR mice following oral administration for 104 weeks.
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.
authors.affiliation: Division 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.
authors.forename: Kyoung-Sik
authors.initials: KS
authors.lastname: Moon
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Hee Su
authors.initials: HS
authors.lastname: Lee
authors.forename: In-Chang
authors.initials: IC
authors.lastname: Hwang
authors.forename: Dal-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Hyun-Kyu
authors.initials: HK
authors.lastname: Park
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Choi
authors.forename: Woori
authors.initials: W
authors.lastname: Jo
authors.forename: Woo-Chan
authors.initials: WC
authors.lastname: Son
authors.forename: Hyo-In
authors.initials: HI
authors.lastname: Yun
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D008297:Male; D008813:Mice, Inbred ICR; D047495:PPAR gamma / Q000819:agonists*; D011743:Pyrimidines / Q000633:toxicity*; D016019:Survival Analysis; D045162:Thiazolidinediones / Q000633:toxicity*; D013997:Time Factors
chemical_list: D002273:Carcinogens; D047495:PPAR gamma; D011743:Pyrimidines; D045162:Thiazolidinediones; C546215:lobeglitazone
keywords: CKD-501; Carcinogenicity; ICR mice·adipocyte proliferation; PPARγ agonist