Role of human flavin-containing monooxygenase (FMO) 5 in the metabolism of nabumetone: Baeyer–Villiger oxidation in the activation of the intermediate metabolite, 3-hydroxy nabumetone, to the active metabolite, 6-methoxy-2-naphthylacetic acid in vitro

References

• Akabane, T., et al., 2011. Case report of extensive metabolism by aldehyde oxidase in humans: pharmacokinetics and metabolite profile of FK3453 in rats, dogs, and humans. Xenobiotica, 41, 372–384.
   PubMed Web of Science ®Google Scholar
• Albertí, J., et al., 2010. Identification of the human enzymes responsible for the enzymatic hydrolysis of aclidinium bromide. Drug metabolism and disposition, 38, 1202–1210.
   PubMed Web of Science ®Google Scholar
• Cashman, J.R., 2008. Role of flavin-containing monooxygenase in drug development. Expert opinion on drug metabolism and toxicology, 4, 1507–1521.
   PubMed Web of Science ®Google Scholar
• Dalvie, D. and Di, L., 2019. Aldehyde oxidase and its role as a drug metabolizing enzyme. Pharmacology and therapeutics, 201, 137–180.
   PubMed Web of Science ®Google Scholar
• Davies, N.M., 1997. Clinical pharmacokinetics of nabumetone. The dawn of selective cyclo-oxygenase-2 inhibition? Clinical pharmacokinetics, 33, 404–416.
   PubMed Web of Science ®Google Scholar
• de Gonzalo, G., Mihovilovic, M.D., and Fraaije, M.W., 2010. Recent developments in the application of Baeyer-Villiger monooxygenases as biocatalysts. Chembiochem, 11, 2208–2231.
   PubMed Web of Science ®Google Scholar
• Fan, P.W., et al., 2016. Going beyond common drug metabolizing enzymes: case studies of biotransformation involving aldehyde oxidase, γ-glutamyl transpeptidase, cathepsin B, flavin-containing monooxygenase, and ADP-ribosyltransferase. Drug metabolism and disposition, 44, 1253–1261.
   PubMed Web of Science ®Google Scholar
• Fiorentini, F., et al., 2017. Baeyer-Villiger monooxygenase FMO5 as entry point in drug metabolism. ACS chemical biology, 12, 2379–2387.
   PubMed Web of Science ®Google Scholar
• Garattini, E., 2012. The role of aldehyde oxidase in drug metabolism. Expert opinion on drug metabolism & toxicology, 8, 487–503.
   PubMed Web of Science ®Google Scholar
• Haddock, R.E., et al., 1984. Metabolism of nabumetone (BRL 14777) by various species including man. Xenobiotica, 14, 327–337.
   PubMed Web of Science ®Google Scholar
• Hausinger, R.P., 2007. New insights into acetone metabolism. Journal of bacteriology, 189, 671–673.
   PubMed Web of Science ®Google Scholar
• Holm, N.B., Noble, C., and Linnet, K., 2016. JWH-018 ω-OH, a shared hydroxy metabolite of the two synthetic cannabinoids JWH-018 and AM-2201, undergoes oxidation by alcohol dehydrogenase and aldehyde dehydrogenase enzymes in vitro forming the carboxylic acid metabolite. Toxicology letters, 259, 35–43.
   PubMed Web of Science ®Google Scholar
• Hou, X., et al., 2018. Differences in the in vivo and in vitro metabolism of imrecoxib in humans: formation of the rate-limiting aldehyde intermediate. Drug metabolism and disposition, 46, 1320–1328.
   PubMed Web of Science ®Google Scholar
• Inoue, K., et al., 2014. Oxidative metabolic pathway of lenvatinib mediated by aldehyde oxidase. Drug metabolism and disposition, 42, 1326–1333.
   PubMed Web of Science ®Google Scholar
• Ishibashi, K., et al., 1989. Metabolism of anti-inflammatory drug, nabumetone, in rat hepatocytes. Drug metabolism and pharmacokinetics, 4, 300–301. (in Japanese).
   Google Scholar
• Isobe, T., et al., 2016. Species differences in metabolism of ripasudil (K-115) are attributed to aldehyde oxidase. Xenobiotica, 46, 579–590.
   PubMed Web of Science ®Google Scholar
• Johnson, C., Stubley-Beedham, C., and Stell, J.G., 1985. Hydralazine: a potent inhibitor of aldehyde oxidase activity in vitro and in vivo. Biochemical pharmacology, 34, 4251–4256.
   PubMed Web of Science ®Google Scholar
• Lai, W.G., et al., 2011. A Baeyer-Villiger oxidation specifically catalyzed by human flavin-containing monooxygenase 5. Drug metabolism and disposition, 39, 61–70.
   PubMed Web of Science ®Google Scholar
• Lam, J.P., Mays, D.C., and Lipsky, J.J., 1997. Inhibition of recombinant human mitochondrial and cytosolic aldehyde dehydrogenases by two candidates for the active metabolites of disulfiram. Biochemistry, 36, 13748–13754.
   PubMed Web of Science ®Google Scholar
• Lee, C.A., et al., 2010. Identification of novel substrates for human cytochrome P450 2J2. Drug metabolism and disposition, 38, 347–356.
   PubMed Web of Science ®Google Scholar
• Leisch, H., Morley, K., and Lau. P.C., 2011. Baeyer-Villiger Monooxygenases: more than just green chemistry. Chemical reviews, 111, 4165–4222.
   PubMed Web of Science ®Google Scholar
• Matsumoto, K., et al., 2015. Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. European journal of drug metabolism and pharmacokinetics, 40, 127–135.
   PubMed Web of Science ®Google Scholar
• Matsumoto, K., et al., 2020. A metabolic pathway for the prodrug nabumetone to the pharmacologically active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA) by non-cytochrome P450 enzymes. Xenobiotica, 50, 783–792.
   PubMed Web of Science ®Google Scholar
• Matsumoto, K., et al., 2011. In vitro characterization of the cytochrome P450 isoforms involved in the metabolism of 6-methoxy-2-napthylacetic acid, an active metabolite of the prodrug nabumetone. Biological and pharmaceutical bulletin, 34, 734–739.
   PubMed Web of Science ®Google Scholar
• Meng, J., et al., 2015. Metabolism of MRX-I, a novel antibacterial oxazolidinone, in humans: the oxidative ring opening of 2,3-Dihydropyridin-4-one catalyzed by non-P450 enzymes. Drug metabolism and disposition, 43, 646–659.
   PubMed Web of Science ®Google Scholar
• Mishin, V., et al., 2010. Application of the amplex red/horseradish peroxidase assay to measure hydrogen peroxide generation by recombinant microsomal enzymes. Free radical biology and medicine, 48, 1485–1491.
   PubMed Web of Science ®Google Scholar
• Nobilis, M., et al., 2013. Analytical power of LLE-HPLC-PDA-MS/MS in drug metabolism studies: identification of new nabumetone metabolites. Journal of pharmaceutical and biomedical analysis, 80, 164–172.
   PubMed Web of Science ®Google Scholar
• Obach, R.S., 2004. Potent inhibition of human liver aldehyde oxidase by raloxifene. Drug metabolism and disposition, 32, 89–97.
   PubMed Web of Science ®Google Scholar
• Oda, S., et al., 2015. A comprehensive review of UDP-glucuronosyltransferase and esterases for drug development. Drug metabolism and pharmacokinetics, 30, 30–51.
   PubMed Web of Science ®Google Scholar
• Ohmi, N., et al., 2003. S-oxidation of S-methyl-esonarimod by flavin-containing monooxygenases in human liver microsomes. Xenobiotica, 33, 1221–1231.
   PubMed Web of Science ®Google Scholar
• Overby, L.H., Carver, G.C., and Philpot, R.M., 1997. Quantitation and kinetic properties of hepatic microsomal and recombinant flavin-containing monooxygenases 3 and 5 from humans. Chemico-biological interactions, 106, 29–45.
   PubMed Web of Science ®Google Scholar
• Panoutsopoulos, G.I., Kouretas, D., and Beedham, C., 2004. Contribution of aldehyde oxidase, xanthine oxidase, and aldehyde dehydrogenase on the oxidation of aromatic aldehydes. Chemical research in toxicology, 17, 1368–1376.
   PubMed Web of Science ®Google Scholar
• Pataki, J., Raddo, P.D., and Harvey, R.G., 1989. An efficient synthesis of the highly tumorigenic anti-diol epoxide derivative of benzo[c]phenanthrene. Journal of organic chemistry, 54, 840–844.
   Web of Science ®Google Scholar
• Phillips, I.R. and Shephard, E.A., 2017. Drug metabolism by flavin-containing monooxygenases of human and mouse. Expert opinion on drug metabolism and toxicology, 13, 167–181.
   PubMed Web of Science ®Google Scholar
• Rodrigues, A.D., 1999. Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes P450 and native human liver microsomes. Biochemical pharmacology, 57, 465–480.
   PubMed Web of Science ®Google Scholar
• Rodrigues, D., et al., 2014. Production of recombinant human aldehyde oxidase in Escherichia coli and optimization of its application for the preparative synthesis of oxidized drug metabolites. ChemCatChem, 6, 1028–1042.
   Web of Science ®Google Scholar
• Siddens, L.K., et al., 2014. Mammalian flavin-containing monooxygenase (FMO) as a source of hydrogen peroxide. Biochemical pharmacology, 89, 141–147.
   PubMed Web of Science ®Google Scholar
• Skarydova, L., Nobilis, M., and Wsól, V., 2013. Role of carbonyl reducing enzymes in the phase I biotransformation of the non-steroidal anti-inflammatory drug nabumetone in vitro. Xenobiotica, 43, 346–354.
   PubMed Web of Science ®Google Scholar
• Strelevitz, T.J., Orozco, C.C., and Obach, R.S., 2012. Hydralazine as a selective probe inactivator of aldehyde oxidase in human hepatocytes: estimation of the contribution of aldehyde oxidase to metabolic clearance. Drug metabolism and disposition, 40, 1441–1448.
   PubMed Web of Science ®Google Scholar
• Takaoka, N., et al., 2018. Inhibitory effects of drugs on the metabolic activity of mouse and human aldehyde oxidases and influence on drug-drug interactions. Biochemical pharmacology, 154, 28–38.
   PubMed Web of Science ®Google Scholar
• Turpeinen, M., et al., 2009. A predominate role of CYP1A2 for the metabolism of nabumetone to the active metabolite, 6-methoxy-2-naphthylacetic acid, in human liver microsomes. Drug metabolism and disposition, 37, 1017–1024.
   PubMed Web of Science ®Google Scholar
• Uzu, S., et al., 1990. Fluorogenic reagents: 4-aminosulphonyl-7-hydrazino-2,1,3-benzoxadiazole,4-(N,N-dimethylaminosulpho-nyl) -7-hydrazino-2,1,3-benzoxadiazole and 4-hydrazino-7-nitro-2,1,3-benzoxadi-azole hydrazine for aldehydes and ketones. Analyst, 115, 1477–1482.
   Web of Science ®Google Scholar
• Varfaj, F., et al., 2014. Carbon-carbon bond cleavage in activation of the prodrug nabumetone. Drug metabolism and disposition, 42, 828–838.
   PubMed Web of Science ®Google Scholar
• Watanabe, A., et al., 2009. Human arylacetamide deacetylase is a principal enzyme in flutamide hydrolysis. Drug metabolism and disposition, 37, 1513–1520.
   PubMed Web of Science ®Google Scholar
• Zhang, J. and Cashman, J.R., 2006. Quantitative analysis of FMO gene mRNA levels in human tissues. Drug metabolism and disposition, 34, 19–26.
   PubMed Web of Science ®Google Scholar