Aldehyde oxidase: An enzyme of emerging importance in drug discovery

Journal of Medicinal Chemistry

Volumn 53, Issue 24, 2010, Pages 8441-8460

  Pryde, David C ^a   Dalvie, Deepak ^b   Hu, Qiyue ^b   Jones, Peter ^a   Obach, R Scott ^b   Tran, Thien Duc ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 CYANOANILINO) 6,7 DIHYDRO 7 HYDROXY 5H CYCLOPENTA[D]PYRIMIDINE; 6 DEOXYPENCICLOVIR; ALDEHYDE OXIDASE; AMSACRINE; ANTINEOPLASTIC AGENT; CARBAZERAN; CHLORPROMAZINE; CIMETIDINE; CYANIDE; DIETHYLSTILBESTROL; ESTRADIOL; ETHINYLESTRADIOL; FAMCICLOVIR; ISOVANILLIN; MEPACRINE; METHADONE; METHOTREXATE; MYRICETIN; N (2 DIMETHYLAMINOETHYL) 4 ACRIDINECARBOXAMIDE; PERPHENAZINE; PROADIFEN; RALOXIFENE; UNCLASSIFIED DRUG; XK 469; ZALEPLON;

ARTICLE; DRUG CLEARANCE; DRUG METABOLISM; DRUG POTENCY; ENZYME STRUCTURE; HUMAN; NONHUMAN; PROTEIN EXPRESSION; SCREENING TEST; STEREOSPECIFICITY; TISSUE DISTRIBUTION;

ALDEHYDE OXIDASE; ANIMALS; DRUG DISCOVERY; HUMANS; MODELS, MOLECULAR; ORGAN SPECIFICITY; OXIDATION-REDUCTION; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS; SPECIES SPECIFICITY; SUBSTRATE SPECIFICITY;

EID: 78650379608     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100888d     Document Type: Article

References (127)

1. Mendel, R. R. Cell biology of molybdenum BioFactors 2009, 35, 429-434
2. Garattini, E.; Fratelli, M.; Terao, M. Mammalian aldehyde oxidases: genetics, evolution and biochemistry Cell. Mol. Life Sci. 2008, 65, 1019-1048
3. Rajagopalan, K. V.; Johnson, J. L. The pterin molybdenum cofactors J. Biol. Chem. 1992, 267, 10199-10202
4. Hille, R. Molybdenum and tungsten in biology Trends Biochem. Sci. 2002, 27, 360-367
5. Garattini, E.; Mendel, R.; Romao, M. J.; Wright, R.; Terao, M. Mammalian molybdo-flavoenzymes, an expanding family of proteins: structure, genetics, regulation, function and pathophysiology Biochem. J. 2008, 372, 15-32
6. Kitamura, S.; Sugihara, K.; Ohta, S. Drug metabolizing ability of molybdenum hydroxylases Drug Metab. Pharmacokinet. 2006, 21, 83-98
7. Krenitsky, T. A.; Neil, S. M.; Elion, G. B.; Hitchings, G. H. A comparison of substrate specificities of xanthine oxidase and aldehyde oxidase Arch. Biochem. Biophys. 1972, 150, 585-599
8. Beedham, C. Molybdenum Hydroxylases. In Enzyme Systems That Metabolise Drugs and Other Xenobiotics; Ioannides, C., Ed.; John Wiley and Sons: London, 2001; pp 147-187.
9. Beedham, C. Molybdenum hydroxylases as drug metabolising enzymes Drug Metab. Rev. 1985, 16, 119-156
10. Kitamura, S.; Sugihara, K.; Nakatani, K.; Ohta, S.; Oh-Hara, T.; Ninomiya, S.; Green, C. E.; Tyson, C. A. Variation of hepatic methotrexate 7-hydroxylase activity in animals and humans IUBMB Life 1999, 48, 607-611
11. Beedham, C.; Bruce, S. E.; Critchley, D. J.; al-Tayib, Y.; Rance, D. J. Species variation in hepatic aldehyde oxidase activity Eur. J. Drug Metab. Pharmacokinet. 1987, 12, 307-310
12. Shimada, S.; Mishima, H. K.; Nikaido, H.; Kitamura, S.; Tatsumi, K. Purification of aldehyde oxidase from bovine ciliary body Curr. Eye Res. 1989, 8, 721-726
13. Moriwaki, Y.; Yamamoto, T.; Takahashi, S.; Tsutsumi, Z.; Hada, T. Widespread cellular distribution of aldehyde oxidase in human tissues found by immunohistochemistry staining Histol. Histopathol. 2001, 16, 745-753
14. Strolin-Benedetti, M.; Whomsley, R.; Baltes, E. Involvement of enzymes other than CYPs in the oxidative metabolism of xenobiotics Expert Opin. Drug Metab. Toxicol. 2006, 2, 895-921
15. Moriwaki, Y.; Yamamoto, T.; Higashino, K. Enzymes involved in purine metabolism. A review of histochemical localization and functional implications Histol. Histopathol. 1999, 14, 1321-1340
16. Kitamura, S.; Nakatani, K.; Ohashi, K.; Sugihara, K.; Hosokawa, R.; Akagawa, Y.; Ohta, S. Extremely high drug reductase activity based on aldehyde oxidase in monkey liver Biol. Pharm. Bull. 2001, 24, 856-859
17. Al-Salmy, H. S. Inter-strain variability in aldehyde oxidase activity in the mouse Comp. Biochem. Physiol., Part C: Toxicol. Pharmacol. 2002, 132, 341-347
18. Sugihara, K.; Kitamura, S.; Tatsumi, K. Strain differences of liver aldehyde oxidase activity in rats Biochem. Mol. Biol. Int. 1995, 37, 861-869
19. Beedham, C. Metabolism of Xenobiotics; Gorrod, J. W.; Oeschlager, H.; Caldwell, J., Eds.; Taylor & Francis: London, 1998; pp 51-58.
20. Stanulovic, M.; Chaykin, S. Aldehyde oxidase: catalysis of the oxidation of N ′-methylnicotinamide and pyridoxal Arch. Biochem. Biophys. 1971, 145, 27-31
21. Rodrigues, A. D. Comparison of levels of aldehyde oxidase with cytochrome P450 activities in human liver in vitro Biochem. Pharmacol. 1994, 48, 197-200
22. Al-Salmy, H. S. Individual variation in hepatic aldehyde oxidase activity IUBMB Life 2001, 51, 249-253
23. Pratt, S. K.; Pue, M. A.; Fairless, A. J.; Fowles, S. E.; Laroche, J.; Kumurav, R.; Prince, W. T. Lack of an effect of gender on the pharmacokinetics of penciclovir following single oral doses of famciclovir Br. J. Clin. Pharmacol. 1994, 37, 493
24. Lavigne, J. The effect of cancer on drug metabolism and drug action Sem. Hop. 1977, 53, 2399-24001
25. Anshar, S.; Puri, R.; Thompson, W.; Habig, W. The effect of interleukin 2 and alpha interferon administration on hepatic drug metabolism in mice Cancer Res. 1992, 52, 262-266
26. Dalvie, D.; Kang, P.; Cho-Ming, L.; Goulet, L.; Nair, S. Influence of Heteroaromatic Rings on ADME Properties of Drugs. In Metabolism, Pharmacokinetics and Toxicity of Functional Groups, 1 st ed.; Smith, D. E., Ed.; RSC Publishing: Cambridge, U.K., 2010; pp 328-369.
27. Brandon, E. F. A.; Christiaan, D.; Raap, C. D.; Meijerman, I.; Jos, H.; Beijnen, J. H.; Schellens, J. H. M. An update on in vitro test methods in human hepatic drug biotransformation research: pros and cons Toxicol. Appl. Pharmacol. 2003, 189, 233-246
28. Obach, R. S. Potent inhibition of human aldehyde oxidase by raloxifene Drug Metab. Dispos. 2004, 32, 89-97
29. Lake, B. G.; Ball, S. E.; Kao, J.; Renwick, A. B.; Price, R. J.; Scatina, J. A. Metabolism of zaleplon by human liver: evidence for involvement of aldehyde oxidase Xenobiotica 2002, 32, 835-847
30. Renwick, A. B.; Ball, S. E.; Tredger, J. M.; Price, R. J.; Walters, D. G.; Kao, J.; Scatina, J. A.; Lake, B. G. Inhibition of zaleplon metabolism by cimetidine in the human liver: in vitro studies with subcellular fractions and precision-cut liver slices Xenobiotica 2002, 32, 849-862
31. Zientek, M.; Jiang, Y.; Youdim, K.; Obach, R. S. In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase Drug Metab. Dispos. 2010, 38, 1322-1327
32. Hille, R. Molybdenum-containing hydroxylases Arch. Biochem. Biophys. 2005, 433, 107-116
33. Alfaro, J. F.; Jones, J. P. Studies on the mechanism of aldehyde oxidase and xanthine oxidase J. Org. Chem. 2008, 73, 9469-9472
34. Torres, R. A.; Korzekwa, K. R.; McMasters, D. R.; Fandozzi, C. M.; Jones, J. P. Use of density functional calculations to predict the regioselectivity of drugs and molecules metabolized by aldehyde oxidase J. Med. Chem. 2007, 50, 4642-4647
35. Guengrich, F. P.; Macdonald, T. L. Chemical mechanisms of catalysis by cytochromes P-450: a unified view Acc. Chem. Res. 1984, 17, 9-16
36. von Ardenne, V. M.; Reitnauer, P. G.; Rieger, F. Zur pharmakokinetik des vitamin-K3-natrium bisulfit als thermosensibilisator fur krebszellen Arch. Geschwulstforsch. 1967, 30, 284-306
37. Johns, D. G. Human liver aldehyde oxidase: differential inhibition of oxidation of charged and uncharged substrates J. Clin. Invest. 1967, 46, 1492-1505
38. Obach, R. S.; Huynh, P.; Allen, M. C.; Beedham, C. Human liver aldehyde oxidase: inhibition by 239 drugs J. Clin. Pharmacol. 2004, 44, 7-19
39. Sahi, J.; Khan, K. K.; Black, C. B. Aldehyde oxidase activity and inhibition in hepatocytes and cytosolic fractions from mouse, rat, monkey and human Drug Metab. Lett. 2008, 2, 176-183
40. Rashidi, M.; Nazemiyeh, H. Inhibitory effects of flavonoids on molybdenum hydroxylases activity Expert Opin. Drug Metab. Toxicol. 2010, 6, 133-152
41. Pirouzpanah, S.; Hanaee, J.; Razavieh, S.; Rashidi, M. Inhibitory effects of flavonoids on aldehyde oxidase activity J. Enzyme Inhib. Med. Chem. 2009, 24, 14-21
42. Johnson, C.; Stubley-Beedham, C.; Stell, J.; Godfrey, P. Hydralazine: a potent inhibitor of aldehyde oxidase activity in vitro and in vivo Biochem. Pharmacol. 1985, 34, 4251-4256
43. Lake, B. G.; Ball, S. E.; Kao, J.; Renwick, A. B.; Price, R. J.; Scatina, J. A. Metabolism of zaleplon by human liver: evidence for involvement of aldehyde oxidase Xenobiotica 2002, 32, 835-847
44. Critchley, D. J. P.; Rance, D. J.; Beedham, C. Biotransformation of carbazeran in guinea pig: effect of hydralazine pretreatment Xenobiotica 1994, 24, 37-47
45. Lee, Y. J.; Chan, K. K. Metabolic interaction between methotrexate and 4′-(9-acridinylamino)methanesulfon- m -anisidide in the rabbit Cancer Res. 1988, 48, 5106-5111
46. Robertson, I. G. C.; Bland, T. J. Inhibition by SKF-525A of the aldehyde oxidase-mediated metabolism of the experimental antitumour agent acridine carboxamide Biochem. Pharmacol. 1993, 45, 2159-2162
47. Schofield, P. C.; Robertson, I. G.; Paxton, J. W. Inter-species variation in the metabolism and inhibition of N -[(2′-dimethylamino)ethyl]acridine- 4-carboxamide (DACA) by aldehyde oxidase Biochem. Pharmacol. 2000, 59, 161-165
48. Gormley, P. E.; Rossitch, E.; D'Anna, M. E.; Cysyk, R. An extremely potent anilinoacridine inhibitor of aldehyde oxidase Biochem. Biophys. Res. Commun. 1983, 116, 759-764
49. Jadhav, A. L.; Bhansali, K. G.; Davis, J. R. 6,6′-Azopurine, a potent in vitro inhibitor of rabbit liver aldehyde oxidase J. Pharm. Sci. 1979, 68, 1202-1203
50. Al-Omar, M. A. In vitro inhibitory effect of quinolinic acid on aldehyde oxidase activity of guinea pig liver: a proposed mechanism Saudi Pharm. J. 2005, 13, 164-170
51. Johns, D. G.; Iannotti, A. T.; Sartorelli, A. C.; Booth, B. A.; Bertino, J. R. Identity of rabbit-liver methotrexate oxidase Biochim. Biophys. Acta 1965, 105, 380-382
52. Felsted, R. L.; Chaykin, S. N 1-Methylnicotinamide oxidation in a number of mammals J. Biol. Chem. 1967, 242, 1274-1279
53. Johns, D. G.; Spector, T.; Robins, R. K. Studies on the mode of oxidation of pyrazolo(3,4- d)pyrimidine by aldehyde oxidase and xanthine oxidase Biochem. Pharmacol. 1969, 18, 2371-2383
54. Clarke, S. E.; Harrell, A. W.; Chenery, R. J. Role of aldehyde oxidase in the in vitro conversion of famciclovir to penciclovir in human liver Drug Metab. Dispos. 1995, 23, 251-254
55. Robertson, I. G. C.; Gamage, R. S. K. A. Methadone: a potent inhibitor of rat liver aldehyde oxidase Biochem. Pharmacol. 1994, 47, 584-587
56. Klecker, R. W.; Cysyk, R. L.; Collins, J. M. Zebularine metabolism by aldehyde oxidase in hepatic cytosol from humans, monkeys, dogs, rats, and mice: influence of sex and inhibitors Bioorg. Med. Chem. 2006, 14, 62-66
57. Ambroziak, W.; Izaguirre, G.; Pietruszko, R. Metabolism of retinaldehyde and other aldehydes in soluble extracts of human liver and kidney J. Biol. Chem. 1999, 274, 33366-33373
58. Beedham, C. Molybdenum hydroxylases: biological distribution and substrate-inhibitor specifity Prog. Med. Chem. 1987, 24, 85-127
59. McDaniel, H. G.; Podgainy, H.; Bressler, R. The metabolism of tolbutamide in rat liver J. Pharmacol. Exp. Ther. 1969, 167, 91-97
60. Ruenitz, P. C.; Bai, X. Acid metabolites of tamoxifen: aspects of formation and fate in the female rat Drug. Metab. Dispos. 1995, 23, 993-998
61. Rochat, B.; Kosel, M.; Goss, G.; Testa, B.; Gillet, M.; Baumann, P. Stereoselective biotransformation of the selective serotonin reuptake inhibitor citalopram and its demethylated metabolites by monoamine oxidases in human liver Biochem. Pharmacol. 1998, 56, 15-23
62. Panoutsopoulos, G. I.; Kouretas, D.; Beedham, C. Contribution of aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase on the oxidation of aromatic aldehydes Chem. Res. Toxicol. 2004, 17, 1368-1376
63. Panoutsopoulos, G. I.; Beedham, C. Kinetics and specificity of guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase towards substituted benzaldehydes Acta Biochim. Pol. 2004, 51, 649-663
64. Panoutsopoulos, G. I.; Beedham, C. Enzymatic oxidation of phthalazine with guinea pig liver aldehyde oxidase and liver slices: inhibition by isovanillin Acta Biochim. Pol. 2004, 51, 943-951
65. Panoutsopoulos, G. I.; Kouretas, D.; Gounaris, E. G.; Beedham, C. Metabolism of 2-phenethylamine and phenacetaldehyde by precision-cut guinea pig fresh liver slices Eur. J. Drug Metab. Pharmacokinet. 2004, 29, 111-118
66. Ghafourian, T.; Rashidi, M. R. Quantitative study of the structural requirements of phthalazine/quinazoline derivatives for interaction with human liver aldehyde oxidase Chem. Pharm. Bull. 2001, 49, 1066-1071
67. Hodnett, C. N.; McCormack, J. J.; Sabean, J. A. Oxidation of selected pteridine derivatives by mammalian liver xanthine oxidase and aldehyde oxidase J. Pharm. Sci. 1976, 65, 1150-1154
68. Austin, N. E.; Baldwin, S. J.; Cutler, L.; Deeks, N.; Kelly, P. J.; Nash, M.; Shardlow, C. E.; Stemp, G.; Thewlis, K.; Ayrton, A.; Jeffrey, P. Pharmacokinetics of the novel, high affinity and selective dopamine D3 receptor antagonist SB-277011 in rat, dog, and monkey: in vitro/in vivo correlation and the role of aldehyde oxidase Xenobiotica 2001, 31, 677-686
69. Moriyasu, A.; Sugihara, K.; Nakatani, K.; Ohta, S.; Kitamura, S. In vivo-in vitro relationship of methotrexate 7-hydroxylation by aldehyde oxidase in four different strain rats Drug Metab. Pharmacokinet. 2006, 21, 485-491
70. Kuroda, T.; Namba, K.; Torimaru, T.; Kawashima, K.; Hayashi, M. Species differences in oral bioavailability of methotrexate between rats and monkeys Biol. Pharm. Bull. 2000, 23, 334-338
71. Rashidi, M. R.; Beedham, C.; Smith, J. S.; Davaran, S. In vitro study of 6-mercaptopurine oxidation catalysed by aldehyde oxidase and xanthine oxidase Drug Metab. Pharmacokinet. 2007, 22, 299-306
72. Zimm, S.; Collins, J. M.; O'Neill, D.; Chabner, B. A.; Poplack, D. G. Inhibition of first-pass metabolism in cancer chemotherapy: interaction of 6-mercaptopurine and allopurinol Clin. Pharmacol. Ther. 1983, 34 (6) 810-817
73. Relling, M. V.; Lin, J. S.; Ayers, G. D.; Evans, W. E. Racial and gender differences in N -acetyltransferase, xanthine oxidase and CYP1A2 activities Clin. Pharmacol. Ther. 1992, 52, 643-658
74. Guo, X.; Lerner-Tung, M.; Hong-Xing, C.; Chang, C.-N.; Zhu, J.-L.; Chang, C.-P.; Pizzorno, G.; Lin, T.-S.; Cheng, Y.-C. 5-Fluoro-2-pyrimidinone, a liver aldehyde oxidase-activated prodrug of 5-fluoro uracil Biochem. Pharmacol. 1995, 49, 1111-1116
75. Porter, D. J. T.; Harrington, J. A.; Almond, M. R.; Lowen, G. T.; Zimmerman, T. P.; Spector, T. 5-Ethynyl-2(1 H)-pyrimidinone: aldehyde oxidase activation to 5-ethynyluracil, a mechanism-based inactivator of dihydropyrimidine dehydrogenase Biochem. Pharmacol. 1994, 47, 1165-1171
76. Krenitsky, T. A.; Hall, W. W.; De Miranda, P.; Beauchamp, L. M.; Schaeffer, H. J.; Whiteman, P. D. 6-Deoxyacyclovir: a xanthine oxidase-activated prodrug of acyclovir Proc. Natl. Acad. Sci. U.S.A. 1984, 81, 3209-3213
77. Moriwaki, Y.; Yamamoto, T.; Nasako, Y.; Takahashi, S.; Suda, M.; Hiroishi, K.; Hada, T.; Higashino, K. In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase Biochem. Pharmacol. 1993, 46, 975-981
78. Yamamoto, T.; Moriwaki, Y.; Suda, M.; Nasako, Y.; Takhashi, S.; Hiroishi, K.; Nakano, T.; Hada, T.; Higashino, K. Effect of BOF-4272 on the oxidation of allopurinol and pyrazinamide in vivo Biochem. Pharmacol. 1993, 46, 2277-2284
79. Robertson, I. G. C.; Palmer, B. D.; Officer, M.; Siegers, D. J.; Paxton, J. W.; Shaw, G. J. Cytosol mediated metabolism of the experimental antitumor agent acridine carboxamide to the 9-acridone derivative Biochem. Pharmacol. 1991, 42, 1879-1884
80. Anderson, L. W.; Collins, J. M.; Klecker, R. W.; Katki, A. G.; Parchment, R. E.; Boinpally, R. R.; LoRusso, P. M.; Ivy, S. P. Metabolic profile of XK469 (2(R)-[4-(7-chloro-2-quinoxalinyl)oxyphenoxy]-propionic acid; NSC698215) in patients and in vitro: low potential for active or toxic metabolites or for drug-drug interactions Cancer Chemother. Pharmacol. 2005, 56, 351-357
81. Furnival, B.; Harrison, J. M.; Newman, J.; Upshall, D. G. The fate of dibenz[ b, f ]-1,4-oxazepine (CR) in the rat. Part II. Metabolism in vitro Xenobiotica 1983, 13, 361-372
82. Acheampong, A. A.; Chien, D.-S.; Lam, S.; Vekich, S.; Breau, A.; Usansky, J.; Harcourt, D.; Munk, S. A.; Nguyen, H.; Garst, M.; Tang-Liu, D. Characterisation of brimonidine metabolism with rat, rabbit, dog, monkey and human liver fractions and rabbit liver aldehyde oxidase Xenobiotica 1996, 26, 1035-1055
83. Jones, P.; Atack, J. R.; Braun, M. P.; Cato, B. P.; Chambers, M. S.; O'Connor, D.; Cook, S. M.; Hobbs, S. C.; Maxey, R.; Szekeres, H. J.; Szeto, N.; Wafford, K. A.; MacLeod, A. M. Pharmacokinetics and metabolism studies on (3- tert -butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1 H -1,2,4-triazol-5- ylmethoxy)pyrazolo[1,5- d ][1,2,4]triazine), a functionally selective GABAA α5 inverse agonist for cognitive dysfunction Bioorg. Med. Chem. Lett. 2006, 16, 872-875
84. O'Connor, D.; Jones, P.; Chambers, M. S.; Maxey, R.; Szekeres, H. J.; Szeto, N.; Scott-Stevens, P.; Macleod, A. M.; Braun, M.; Cato, B. Aldehyde oxidase and its contribution to the metabolism of a structurally novel, functionally selective GABAA α5 subtype inverse agonist Xenobiotica 2006, 36, 315-330
85. Tran, T.-D.; Adam, F. M.; Calo, F.; Fenwick, D. R.; Fok-Seang, J.; Gardner, I.; Hay, D. A.; Perros, M.; Rawal, J.; Middleton, D. S.; Parkinson, T.; Pickford, C.; Platts, M.; Randall, A.; Stephenson, P. T.; Vuong, H.; Williams, D. H. Design and optimization of potent gp120-CD4 inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 5250-5255
86. Brandaenge, S.; Lindblom, L. The enzyme "aldehyde oxidase" is an iminium oxidase. Reaction with nicotine Δ1′(5′) iminium ion Biochem. Biophys. Res. Commun. 1979, 91, 991-996
87. Rodrigues, A. D.; Ferrero, J. L.; Amann, M. T.; Rotert, G. A.; Cepa, S. P.; Surber, B. W.; Machinist, J. M.; Tich, N. R.; Sullivan, J. P. The in vitro hepatic metabolism of ABT-418, a cholinergic channel activator, in rats, dogs, cynomolgous monkeys, and humans Drug Metab. Dispos. 1994, 22, 788-798
88. Whittlesea, C. M. C.; Gorrod, J. W. The enzymology of the in vitro oxidation of prolintane to oxoprolintane J. Clin. Pharm. Ther. 1993, 18, 357-364
89. Stanulovic, M.; Chaykin, S. Aldehyde oxidase. Catalysis of the oxidation of N 1-methylnicotinamide and pyridoxal Arch. Biochem. Biophys. 1971, 145, 27-34
90. Itoh, K.; Yamamura, M.; Muramatsu, S.; Hoshino, K.; Masubuchi, A.; Sasaki, T.; Tanaka, Y. Stereospecific oxidation of the (S)-enantiomer of RS-8359, a selective and reversible monoamine oxidase A (MAO-A) inhibitor, by aldehyde oxidase Xenobiotica 2005, 35, 561-571
91. Takasaki, W.; Yamamura, M.; Nozaki, A.; Nitanai, T.; Sasahara, K.; Itoh, K.; Tanaka, Y. Stereoselective pharmacokinetics of RS-8359, a selective and reversible MAO-A inhibitor, by species-dependent drug-metabolizing enzymes Chirality 2005, 17, 135-141
92. Nakasa, H.; Komiya, M.; Ohmori, S.; Rikihisa, T.; Kiuchi, M.; Kitada, M. Characterization of human liver microsomal cytochrome P450 involved in the reductive metabolism of zonisamide. Mol. Pharmacol. 1993, 44 (1), 216-221 and references therein.
93. Kitamura, S.; Tatsumi, K. Involvement of liver aldehyde oxidase in the reduction of nicotinamide N -oxide Biochem. Biophsy. Res. Commun. 1984, 120, 602-606
94. Kitamura, S.; Tatsumi, K. Reduction of tertiary amine N -oxides by liver preparations: function of aldehyde oxidase as a major N -oxide reductase Biochem. Biophys. Res. Commun. 1984, 121, 749-754
95. Tatsumi, K.; Kitamura, S.; Hiroshi, Y. Involvement of liver aldehyde oxidase in sulfoxide reduction Chem. Pharm. Bull. 1982, 30, 4585-4588
96. Kitamura, S.; Suzuki, T.; Kadota, T.; Yoshida, M.; Ohashi, K.; Ohta, S. In vitro metabolism of fenthion and fenthion sulfoxide by liver preparations of sea bream, goldfish and rats Drug Metab. Dispos. 2003, 31, 179-186
97. Dick, R. A.; Kanne, D. B.; Casida, J. E. Substrate specificity of rabbit aldehyde oxidase for nitroguanidine and nitromethylene neonicotinoid insecticides Chem. Res. Toxicol. 2006, 19, 38-43
98. Dick, R. A.; Kanne, D. B.; Casida, J. E. Identification of aldehyde oxidase as the neonicotinoid nitroreductase Chem. Res. Toxicol. 2005, 18, 317-323
99. Beedham, C.; Miceli, J.; Obach, R. S. Ziprasidone metabolism, aldehyde oxidase, and clinical implications J. Clin. Psychopharmacol. 2003, 23, 229-232
100. Miao, Z.; Kamel, A.; Prakash, C. Characterization of a novel metabolite intermediate of ziprasidone in hepatic cytosolic fractions of rat, dog and human by ESI-MS/MS, hydrogen deuterium exchange and chemical derivatization Drug Metab. Dispos. 2005, 33, 879-883
101. Sugihara, K.; Kitamura, S.; Tatsumi, K. Involvement of mammalian liver cytosols and aldehyde oxidase in reductive metabolism of zonisamide Drug Metab. Dispos. 1996, 24, 199-202
102. Kaye, B.; Rance, D. J.; Waring, L. Oxidative metabolism of carbazeran in vitro by liver cytosol of baboon and man Xenobiotica 1985, 15, 237-242
103. Magee, T. V.; Ripp, S. L.; Li, B.; Buzon, R. A.; Chupak, L.; Dougherty, T. J.; Finegan, S. M.; Girard, D.; Hagen, A. E.; Falcone, M. J.; Farley, K. A.; Granskog, K.; Hardink, J. R.; Huband, M. D.; Kamicker, B. J.; Kaneko, T.; Knickerbocker, M. J.; Liras, J. L.; Marra, A.; Medina, I.; Nguyen, T.-T.; Noe, M. C.; Obach, R. S.; O'Donnell, J. P.; Penzien, J. B.; Reilly, U. D.; Schafer, J. R.; Shen, Y.; Stone, G. G.; Strelevitz, T. J.; Sun, J.; Tait-Kamradt, A.; Vaz, A. D. N.; Whipple, D. A.; Widlicka, D. W.; Wishka, D. G.; Wolkowski, J. P.; Flanagan, M. E. Discovery of azetidinyl ketolides for the treatment of susceptible and multidrug resistant community-acquired respiratory tract infections J. Med. Chem. 2009, 52, 7446-7457
104. Zhang, X.; Liu, H.-H.; Weller, P.; Zheng, M.; Tao, W.; Wang, J.; Liao, G.; Monshouwer, M.; Peltz, G. In silico and in vitro pharmacogenetics: aldehyde oxidase rapidly metabolizes a p38 kinase inhibitor. Pharmacogenomics J. [Online early access]. DOI: 10.1038/tpj.2010.8. Published Online: Feb 23, 2010.
105. Chaudhary, I.; DeMaio, W.; Kantrowitz, J. Species comparison of in vitro and in vivo metabolism of CL284,846, a non-benzodiazepine sedative/hypnotic agent Pharm. Res. (N.Y.) 1994, 11, 319
106. Kawashima, K.; Hosoi, K.; Naruke, T.; Shiba, T.; Kitamura, M.; Watabe, T. Aldehyde oxidase-dependant marked species difference in hepatic metabolism of the sedative-hypnotic, zaleplon, between monkeys and rats Drug Metab. Dispos. 1999, 27, 422-428
107. Rashidi, M. R.; Smith, J. A.; Clarke, S. E.; Beedham, C. In vitro oxidation of famciclovir and 6-deoxypenciclovir by aldehyde oxidase from human, guinea pig, rabbit, and rat liver Drug Metab. Dispos. 1997, 25, 805-813
108. Filer, C. W.; Ramji, J. V.; Allen, G. D.; Brown, T. A.; Fowles, S. E.; Hollis, F. J.; Mort, E. E. Metabolic and pharmacokinetic studies following oral administration of famciclovir to the rat and dog Xenobiotica 1995, 25, 477-490
109. Angelino, S. A. G. F.; van Veldhuizen, A.; Buurman, D. J.; van der Plas, H. C. Covalent amination of 1-alkyl-and 1-aryl-3-carbamoylpyridinium chlorides as "model" for enzymatic activity of rabbit liver aldehyde oxidase Tetrahedron 1984, 40, 433-439
110. Dastmalchi, S.; Hamzeh-Mivehrod, M. Molecular modelling of human aldehyde oxidase and the identification of the key interactions in the enzyme-substrate complex Daru, J. Fac. Pharm., Tehran Univ. Med. Sci. 2005, 13, 82-93
111. Okamoto, K.; Matsumoto, K.; Hille, R.; Eger, B. T.; Pai, E. F.; Nishino, T. The crystal structure of xanthine oxidoreductase during catalysis: implications for reaction mechanism and enzyme inhibition Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 7931-7936
112. Kola, I.; Landis, J. Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug Discovery 2004, 3, 711-716
113. Beaumont, K.; Smith, D. Does human pharmacokinetic prediction add significant value to compound selection in drug discovery research? Curr. Opin. Drug Discovery Dev. 2009, 12, 61-71
114. Imming, P.; Sinning, C.; Meyer, A. Drugs, their targets and the nature and number of drug targets Nat. Rev. Drug Discovery 2006, 5, 821-834
115. Muller, G.; Klebl, B. Second-generation kinase inhibitors Expert Opin. Ther. Targets 2005, 9, 975-993
116. Treherne, J. Exploiting high-throughput ion channel screening technologies in integrated drug discovery Curr. Pharm. Des. 2006, 12, 397-406
117. Yeap, S.; Walley, R.; Snarey, M.; Van Hoorn, W.; Mason, J. Designing compound subsets: comparison of random and rational approaches using statistical simulation J. Chem. Inf. Model. 2007, 47, 2149-2158
118. Klabunde, T.; Hessler, G. G-Protein coupled receptors: drug design strategies Wiley Encycl. Chem. Biol. 2009, 2, 211-231
119. Alton, G.; Lunney, E. Targeting the unactivated conformations of protein kinases for small molecule drug discovery Expert Opin. Drug Discovery 2008, 3, 595-605
120. Knight, Z.; Shokat, K. Features of selective kinase inhibitors Chem. Biol. 2005, 12, 621-637
121. Liu, Y.; Gray, N. Rational design of inhibitors that bind to inactive kinase conformations Nat. Chem. Biol. 2006, 2, 358-364
122. Moriwaki, Y.; Yamamoto, T.; Higashino, K. Distribution and pathophysiologic role of molybdenum-containing enzymes Histol. Histopathol. 1997, 12, 513-524
123. Diamond, S.; Boer, J.; Maduskuie, T.; Falahatpisheh, N; Li, Y.; Yeleswaram, S. Species-specific metabolism of SGX523 by aldehyde oxidase and the toxicological implications Drug Metab. Dispos. 2010, 38, 1277-1285
124. Berger, R.; Mezey, E.; Clancy, K.; Harta, G.; Wright, R.; Repine, J.; Brown, R.; Brownstein, M.; Patterson, D. Analysis of aldehyde oxidase and xanthine dehydrogenase/oxidase as possible candidate genes for autosomal recessive familial amyotrophic lateral sclerosis Somatic Cell Mol. Genet. 1995, 21, 121-131
125. Sharma, R.; Strelevitz, T. J.; Gao, H.; Clark, A. J.; Schildknegt, K.; Obach, R. S.; Ripp, S. L.; Tremaine, L. M.; Spracklin, D. K.; Vaz, A. D. N. Deuterated drugs: importance of the clearance mechanism when applying kinetic deuterium isotope effects to pharmacokinetics. Manuscript submitted.
126. Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shelley, M.; Perry, J. K.; Shaw, D. E.; Francis, P.; Shenkin, P. S. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy J. Med. Chem. 2004, 47, 1739-1749
127. HLM stability was calculated using an in-house model based on MOE descriptors. E-state, cLogP, and structural fragments were coded in MOE. See the following: MOE, version 2009.10; Chemical Computing Group Inc.: Montreal, Canada; www.chemcomp.com.