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| | {{STRUCTURE_1vdv| PDB=1vdv | SCENE= }} | | {{STRUCTURE_1vdv| PDB=1vdv | SCENE= }} |
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| - | '''Bovine Milk Xanthine Dehydrogenase Y-700 Bound Form'''
| + | ===Bovine Milk Xanthine Dehydrogenase Y-700 Bound Form=== |
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| - | ==Overview==
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| - | Y-700 (1-[3-Cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid) is a newly synthesized inhibitor of xanthine oxidoreductase (XOR). Steady-state kinetics with the bovine milk enzyme indicated a mixed type inhibition with K(i) and K(i) ' values of 0.6 and 3.2 nM, respectively. Titration experiments showed that Y-700 bound tightly both to the active sulfo-form and to the inactive desulfo-form of the enzyme with K(d) values of 0.9 and 2.8 nM, respectively. X-ray crystallographic analysis of the enzyme-inhibitor complex revealed that Y-700 closely interacts with the channel leading to the molybdenum-pterin active site but does not directly coordinate to the molybdenum ion. In oxonate-treated rats, orally administered Y-700 (1-10 mg/kg) dose dependently lowered plasma urate levels. At a dose of 10 mg/kg, the hypouricemic action of Y-700 was more potent and of longer duration than that of 4-hydroxypyrazolo(3,4-d)pyrimidine, whereas its action was approximately equivalent to that of 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid, a nonpurine inhibitor of XOR. In normal rats, orally administered Y-700 (0.3-3 mg/kg) dose dependently reduced the urinary excretion of urate and allantoin, accompanied by an increase in the excretion of hypoxanthine and xanthine. Y-700 (1 mg/kg) was absorbed rapidly by the oral route with high bioavailability (84.1%). Y-700 was hardly excreted via the kidneys but was mainly cleared via the liver. These results suggest that Y-700 will be a promising candidate for the treatment of hyperuricemia and other diseases in which XOR may be involved.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_15190124}}, adds the Publication Abstract to the page |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Xanthine oxidoreductase]] | | [[Category: Xanthine oxidoreductase]] |
| | [[Category: Y-700]] | | [[Category: Y-700]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:25:19 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:56:10 2008'' |
Revision as of 11:56, 28 July 2008
Template:STRUCTURE 1vdv
Bovine Milk Xanthine Dehydrogenase Y-700 Bound Form
Template:ABSTRACT PUBMED 15190124
About this Structure
1VDV is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
Y-700 [1-[3-Cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid]: a potent xanthine oxidoreductase inhibitor with hepatic excretion., Fukunari A, Okamoto K, Nishino T, Eger BT, Pai EF, Kamezawa M, Yamada I, Kato N, J Pharmacol Exp Ther. 2004 Nov;311(2):519-28. Epub 2004 Jun 9. PMID:15190124
Page seeded by OCA on Mon Jul 28 14:56:10 2008
