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In Vitro Metabolism of a New Cardioprotective Agent, KR-33028 in the Human Liver Microsomes and Cryopreserved Human Hepatocytes  

Kim Hyojin (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine)
Yoon Yune-Jung (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine)
Kim Hyunmi (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine)
Cha Eun-Young (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine)
Lee Hye Suk (Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University)
Kim Jeong-Han (School of Agricultural Biotechnology, Seoul National University)
Yi Kyu Yang (Bio-organic Science Division, Korea Research Institute of Chemical Technology)
Lee Sunkyung (Bio-organic Science Division, Korea Research Institute of Chemical Technology)
Cheon Hyae Gyeong (Bio-organic Science Division, Korea Research Institute of Chemical Technology)
Yoo Sung-Eun (Bio-organic Science Division, Korea Research Institute of Chemical Technology)
Lee Sang-Seop (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine)
Shin Jae-Gook (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine)
Liu Kwang-Hyeon (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine)
Publication Information
Archives of Pharmacal Research / v.28, no.11, 2005 , pp. 1287-1292 More about this Journal
Abstract
KR-33028 (N-[4-cyano-benzo[b]thiophene-2-carbonyl]guanidine) is a new cardioprotective agent for preventing ischemia-reperfusion injury. This study was performed to identify the metabolic pathway of KR-33028 in human liver microsomes and to compare its metabolism with that of cryopreserved human hepatocytes. Human liver microsomal incubation of KR-33028 in the presence of NADPH and UDPGA resulted in the formation of four metabolites, M1, M2, M3, and M4. M1 and M2 were identified as 5-hydroxy-KR-33028 and 7-hydroxy-KR-33028, respectively, on the basis of LC/MS/MS analysis with the synthesized authentic standard. M3 and M4 were suggested to be dihydroxy-KR-33028 and hydroxy-KR-33028-glucuronide, respectively. Metabolism of KR-33028 in cryopreserved human hepatocytes resulted in the formation of M1, M2, and M4. These data show a good correlation between major metabolites formed in human liver microsomes and cryopreserved human hepatocytes. In addition, KR­33028 was found to inhibit moderately the metabolism of CYP1A2 substrates. Based on the results obtained metabolic pathway of KR-33028 is proposed.
Keywords
KR-33028; Metabolism; Microsomes; Hepatocytes; LC/MS/MS;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
Times Cited By Web Of Science : 5  (Related Records In Web of Science)
Times Cited By SCOPUS : 5
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