Yanting Wu1,2, Menghe Li1,2, Yuying Guo3, Tao Liu1,2, Lishan Zhong1,2, Chen Huang1,2, Cuifang Ye1,2, Qiuying Liu1,2,4, Zhe Ren1,2, Yifei Wang5,6,7. 1. Department of Cell Biology, College of Life Science and Technology, Jinan University, No. 601, Whampoa Road West, Guangzhou, 510632, People's Republic of China. 2. Department of Cell Biology, Guangdong Province Key Laboratory of Bioengineering Medicine, Guangdong Provincial Biotechnology Drug & Engineering Technology Research Center, National Engineering Research Center of Genetic Medicine, Guangzhou, People's Republic of China. 3. Department of Cell Biology, Guangzhou Jinan Biomedicine Research and Development Center Co. Ltd, Guangzhou, People's Republic of China. 4. Department of pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China. 5. Department of Cell Biology, College of Life Science and Technology, Jinan University, No. 601, Whampoa Road West, Guangzhou, 510632, People's Republic of China. twang-yf@163.com. 6. Department of Cell Biology, Guangdong Province Key Laboratory of Bioengineering Medicine, Guangdong Provincial Biotechnology Drug & Engineering Technology Research Center, National Engineering Research Center of Genetic Medicine, Guangzhou, People's Republic of China. twang-yf@163.com. 7. Department of Cell Biology, Guangzhou Jinan Biomedicine Research and Development Center Co. Ltd, Guangzhou, People's Republic of China. twang-yf@163.com.
Abstract
BACKGROUND AND OBJECTIVES: AT-533 is a novel heat shock protein 90 inhibitor, which exhibits various biological activities in vitro and in vivo. Cytochrome P450 (CYP) enzymes in the liver are involved in the biotransformation of drugs and considered to be essential indicators of liver toxicity. The aim of this study was to assess the effect of AT-533, either as active pharmaceutical ingredient or in gel form, on liver CYP enzymes. METHODS: The effect of AT-533 or AT-533 gel on rat liver cytochrome P450 enzymes, including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, was analyzed using LC-MS/MS. RESULTS: AT-533 and AT-533 gel did not significantly increase or reduce the enzymatic activity of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 at any treatment dose. CONCLUSIONS: AT-533 and AT-533 gel did not have any effect on CYP activity and may be considered safe for external use in gel form, as an alternative to conventional treatment.
BACKGROUND AND OBJECTIVES: AT-533 is a novel heat shock protein 90 inhibitor, which exhibits various biological activities in vitro and in vivo. Cytochrome P450 (CYP) enzymes in the liver are involved in the biotransformation of drugs and considered to be essential indicators of liver toxicity. The aim of this study was to assess the effect of AT-533, either as active pharmaceutical ingredient or in gel form, on liver CYP enzymes. METHODS: The effect of AT-533 or AT-533 gel on rat liver cytochrome P450 enzymes, including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, was analyzed using LC-MS/MS. RESULTS: AT-533 and AT-533 gel did not significantly increase or reduce the enzymatic activity of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 at any treatment dose. CONCLUSIONS: AT-533 and AT-533 gel did not have any effect on CYP activity and may be considered safe for external use in gel form, as an alternative to conventional treatment.
Authors: So Young Park; Chung Hyeon Kim; Ji Yoon Lee; Jang Su Jeon; Min Ju Kim; Song Hee Chae; Hyoung Chin Kim; Soo Jin Oh; Sang Kyum Kim Journal: Food Chem Toxicol Date: 2016-08-11 Impact factor: 6.023
Authors: J Andrew Williams; Ruth Hyland; Barry C Jones; Dennis A Smith; Susan Hurst; Theunis C Goosen; Vincent Peterkin; Jeffrey R Koup; Simon E Ball Journal: Drug Metab Dispos Date: 2004-08-10 Impact factor: 3.922