title: Carcinogenicity study of CKD-501, a novel dual peroxisome proliferator-activated receptors α and γ agonist, following oral administration to Sprague Dawley rats for 94-101 weeks.
abstract: CKD-501 is a peroxisome proliferator-activated receptor (PPAR) agonist. The current study was conducted in Sprague Dawley (SD) rats for 94-101 weeks to investigate the carcinogenic potential of CKD-501. 60 males received 0, 0.03, 0.12, or 1.0mg/kg/day, which was changed after 66 weeks to 0.24 mg/kg/day due to increased mortality, while 60 females received 0, 0.03, 0.06, or 0.12 mg/kg/day throughout the study period. After switching the dosage, no significant changes in the survival rates were observed. Non-neoplastic lesions such as bladder transitional cell hyperplasia and a diminished corpus luteum were observed in females administered 0.12 mg/kg/day and the right chamber dilation and left ventricular hypertrophy were increased dose dependently in both males and females. Non-neoplastic lesions such as bone marrow hypoplasia and fat cell proliferation and neoplastic lesions such as lipomas and liposarcomas observed in males and/or females were considered expected pharmacological effects for this compound. Compared to rosiglitazone, CKD-501 had a 4.4-fold higher margin of safety for tumor induction and did not cause bladder carcinoma as was observed with pioglitazone.
authors.affiliation: Department of Pathology, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Hee Su
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Medical and Pharmaceutical Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Minsun
authors.initials: M
authors.lastname: Chang
authors.affiliation: Department of Pathology, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Pathology, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Woojin
authors.initials: W
authors.lastname: Kim
authors.affiliation: Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., Kyunggi-do, Republic of Korea.
authors.forename: In-Chang
authors.initials: IC
authors.lastname: Hwang
authors.affiliation: Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., Kyunggi-do, Republic of Korea.
authors.forename: Dal-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Hyun-Kyu
authors.initials: HK
authors.lastname: Park
authors.affiliation: Department of Pathology, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Pathology, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Woori
authors.initials: W
authors.lastname: Jo
authors.affiliation: Division of Non-clinical Studies, Korea Institute of Toxicology (KIT), Daejeon, Republic of Korea.
authors.forename: Shin-Woo
authors.initials: SW
authors.lastname: Cha
authors.affiliation: Department of Pathology, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. Electronic address: wcson@amc.seoul.kr.
authors.forename: Woo-Chan
authors.initials: WC
authors.lastname: Son
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008067:Lipoma / Q000139:chemically induced* / Q000473:pathology; D008080:Liposarcoma / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010976:Platelet Count; D011743:Pyrimidines / Q000008:administration & dosage* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000633:toxicity*; D013997:Time Factors
chemical_list: D002273:Carcinogens; D047493:PPAR alpha; D047495:PPAR gamma; D011743:Pyrimidines; D045162:Thiazolidinediones; C546215:lobeglitazone
keywords: CKD-501; Carcinogenicity; Dual PPARα/γ agonist