CYP2C76, a novel cytochrome P450 in cynomolgus monkey, is a major CYP2C in liver, metabolizing tolbutamide and testosterone

Molecular Pharmacology
Yasuhiro UnoRyoichi Nagata

Abstract

Monkeys are widely used as a primate model to study drug metabolism because they generally show a metabolic pattern similar to humans. However, the paucity of information on cytochrome P450 (P450) genes has hampered a deep understanding of drug metabolism in the monkey. In this study, we report identification of the CYP2C76 cDNA newly identified in cynomolgus monkey and characterization of this CYP2C along with cynomolgus CYP2C20, CYP2C43, and CYP2C75. The CYP2C76 cDNA contains the open reading frame encoding a protein of 489 amino acids that are only approximately 80% identical to any human or monkey P450 cDNAs. Gene and protein expression of CYP2C76 was confirmed in the liver of cynomolgus and rhesus monkeys but not in humans or the great apes. Moreover, CYP2C76 is located at the end of the CYP2C gene cluster in the monkey genome, the region of which corresponds to the intergenic region adjacent to the CYP2C cluster in the human genome, strongly indicating that this gene does not have the ortholog in humans. Among the four CYP2C genes expressing predominantly in the liver, the expression level of CYP2C76 was the greatest, suggesting that CYP2C76 is a major CYP2C in the monkey liver. Assays for the capacity of CYP2C76 to metab...Continue Reading

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Citations

Apr 30, 2010·Pharmaceutical Research·Cuyue Tang, Thomayant Prueksaritanont
Aug 19, 2011·The Journal of Pharmacology and Experimental Therapeutics·Shotaro UeharaYasuhiro Uno
Nov 27, 2009·The Journal of Veterinary Medical Science·Yasuhiro UnoHiroshi Yamazaki
Nov 26, 2010·The Journal of Veterinary Medical Science·Yasuhiro UnoHiroshi Yamazaki
Jan 29, 2011·Drug Metabolism and Pharmacokinetics·Yasuharu NakanishiYasuhiro Uno
Jan 29, 2011·Drug Metabolism and Pharmacokinetics·Ryota IseYasuhiro Uno
Mar 9, 2011·Drug Metabolism and Pharmacokinetics·Haruka NishimutaSetsuko Komuro
Aug 17, 2011·Drug Metabolism and Pharmacokinetics·Ryota IseYasuhiro Uno
Feb 10, 2011·Drug Metabolism Reviews·Yasuhiro UnoDavid R Nelson
Jul 23, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·K Iwasaki, Y Uno
Oct 12, 2010·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Shotaro UeharaYasuhiro Uno
Jul 16, 2008·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Brett R JonesRoss A McKinnon
Jan 16, 2007·Biochemical Pharmacology·Cuyue TangBrian A Carr
Jun 10, 2011·Basic & Clinical Pharmacology & Toxicology·Yasuhiro UnoHiroshi Yamazaki
Feb 14, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Noriaki YodaEiji Kashiyama
Mar 7, 2014·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Shotaro UeharaYasuhiro Uno
May 18, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Masahiro UtohHiroshi Yamazaki
Dec 31, 2014·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Gaku OkamatsuHiroki Teraoka
Nov 30, 2011·Drug Metabolism and Pharmacokinetics·Shotaro UeharaYasuhiro Uno
May 8, 2013·Drug Metabolism and Pharmacokinetics·Yasuharu NakanishiYasuhiro Uno
May 9, 2014·Drug Metabolism and Pharmacokinetics·Yasuhiro UnoKazuhide Iwasaki
Jul 9, 2010·Drug Metabolism and Pharmacokinetics·Yasuharu NakanishiYasuhiro Uno
Oct 9, 2012·Biochemical Pharmacology·Yoshio HosoiHiroshi Yamazaki
Apr 30, 2013·Biochemical Pharmacology·Yasuhiro UnoHiroshi Yamazaki
Jul 6, 2013·Biochemical Pharmacology·Yasuhiro UnoHiroshi Yamazaki
Mar 12, 2015·Drug Metabolism and Pharmacokinetics·Yasuhiro UnoHiroshi Yamazaki
Mar 25, 2015·Biochemical Pharmacology·Masahiro UtohHiroshi Yamazaki
Oct 10, 2015·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Mauro LeonciniKarina Panucia Tillan
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Jul 29, 2017·Journal of Veterinary Pharmacology and Therapeutics·Y UnoH Yamazaki
Mar 25, 2018·Journal of Medical Primatology·Yasuhiro UnoTeruko Imai
Aug 17, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yasuhiro Uno, Hiroshi Yamazaki
Jun 1, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yuka OnoHiroki Teraoka
Sep 15, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yasuhiro UnoHiroshi Yamazaki
Feb 1, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yasuhiro UnoTeruko Imai
Oct 1, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yasuhiro UnoRyoichi Nagata

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