Carcinogenicity study of CKD-501, a novel dual peroxisome proliferator-activated receptors alpha and gamma agonist, following oral administration to Sprague Dawley rats for 94-101 weeks
  • Lee, Hee Su
  • Chang, Minsun
  • Lee, Ji-Eun
  • Kim, Woojin
  • Hwang, In-Chang
  • 외 6명
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초록

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 1.0 mg/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. (C) 2014 Elsevier Inc. All rights reserved.

키워드

CKD-501CarcinogenicityDual PPAR alpha/gamma agonistPPAR-GAMMARODENT CARCINOGENICITYTHIAZOLIDINEDIONETROGLITAZONEGLUCOSE
제목
Carcinogenicity study of CKD-501, a novel dual peroxisome proliferator-activated receptors alpha and gamma agonist, following oral administration to Sprague Dawley rats for 94-101 weeks
저자
Lee, Hee SuChang, MinsunLee, Ji-EunKim, WoojinHwang, In-ChangKim, Dal-HyunPark, Hyun-KyuChoi, Hyun-JiJo, WooriCha, Shin-WooSon, Woo-Chan
DOI
10.1016/j.yrtph.2014.04.003
발행일
2014-07
유형
Article
저널명
Regulatory Toxicology and Pharmacology
69
2
페이지
207 ~ 216