Target Information
Target General Infomation | |||||
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Target ID |
T40954
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Former ID |
TTDS00056
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Target Name |
Xanthine dehydrogenase/oxidase
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Gene Name |
XDH
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Synonyms |
Xanthine oxidase; XDH
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Target Type |
Successful
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Disease | Cancer [ICD9: 140-229; ICD10: C00-C96] | ||||
Encephalopathy [ICD10: G93.4] | |||||
Gout [ICD9: 274.00274.1274.8274.9; ICD10: M10] | |||||
Hyperuricemia [ICD9: 790.6; ICD10: E79.0] | |||||
Hyperuricaemia in gout [ICD9: 274, 790.6; ICD10: E79.0, M10] | |||||
Heart failure [ICD9: 428; ICD10: I50] | |||||
Function |
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
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BioChemical Class |
Oxidoreductases acting on CH or CH(2) groups
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Target Validation |
T40954
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UniProt ID | |||||
EC Number |
EC 1.17.3.2
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Sequence |
MTADKLVFFVNGRKVVEKNADPETTLLAYLRRKLGLSGTKLGCGEGGCGACTVMLSKYDR
LQNKIVHFSANACLAPICSLHHVAVTTVEGIGSTKTRLHPVQERIAKSHGSQCGFCTPGI VMSMYTLLRNQPEPTMEEIENAFQGNLCRCTGYRPILQGFRTFARDGGCCGGDGNNPNCC MNQKKDHSVSLSPSLFKPEEFTPLDPTQEPIFPPELLRLKDTPRKQLRFEGERVTWIQAS TLKELLDLKAQHPDAKLVVGNTEIGIEMKFKNMLFPMIVCPAWIPELNSVEHGPDGISFG AACPLSIVEKTLVDAVAKLPAQKTEVFRGVLEQLRWFAGKQVKSVASVGGNIITASPISD LNPVFMASGAKLTLVSRGTRRTVQMDHTFFPGYRKTLLSPEEILLSIEIPYSREGEYFSA FKQASRREDDIAKVTSGMRVLFKPGTTEVQELALCYGGMANRTISALKTTQRQLSKLWKE ELLQDVCAGLAEELHLPPDAPGGMVDFRCTLTLSFFFKFYLTVLQKLGQENLEDKCGKLD PTFASATLLFQKDPPADVQLFQEVPKGQSEEDMVGRPLPHLAADMQASGEAVYCDDIPRY ENELSLRLVTSTRAHAKIKSIDTSEAKKVPGFVCFISADDVPGSNITGICNDETVFAKDK VTCVGHIIGAVVADTPEHTQRAAQGVKITYEELPAIITIEDAIKNNSFYGPELKIEKGDL KKGFSEADNVVSGEIYIGGQEHFYLETHCTIAVPKGEAGEMELFVSTQNTMKTQSFVAKM LGVPANRIVVRVKRMGGGFGGKETRSTVVSTAVALAAYKTGRPVRCMLDRDEDMLITGGR HPFLARYKVGFMKTGTVVALEVDHFSNVGNTQDLSQSIMERALFHMDNCYKIPNIRGTGR LCKTNLPSNTAFRGFGGPQGMLIAECWMSEVAVTCGMPAEEVRRKNLYKEGDLTHFNQKL EGFTLPRCWEECLASSQYHARKSEVDKFNKENCWKKRGLCIIPTKFGISFTVPFLNQAGA LLHVYTDGSVLLTHGGTEMGQGLHTKMVQVASRALKIPTSKIYISETSTNTVPNTSPTAA SVSADLNGQAVYAACQTILKRLEPYKKKNPSGSWEDWVTAAYMDTVSLSATGFYRTPNLG YSFETNSGNPFHYFSYGVACSEVEIDCLTGDHKNLRTDIVMDVGSSLNPAIDIGQVEGAF VQGLGLFTLEELHYSPEGSLHTRGPSTYKIPAFGSIPIEFRVSLLRDCPNKKAIYASKAV GEPPLFLAASIFFAIKDAIRAARAQHTGNNVKELFRLDSPATPEKIRNACVDKFTTLCVT GVPENCKPWSVRV |
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Drugs and Mode of Action | |||||
Drug(s) | Allopurinol | Drug Info | Approved | Hyperuricemia | [538511], [541876] |
Febuxostat | Drug Info | Approved | Hyperuricaemia in gout | [530677], [541899] | |
Curcumin | Drug Info | Phase 3 | Cancer | [532348], [542031] | |
Oxypurinol | Drug Info | Phase 2/3 | Heart failure | [521563] | |
Cyclic pyranopterin monophosphate | Drug Info | Phase 2 | Encephalopathy | [524617] | |
Topiroxostat | Drug Info | Phase 2 | Gout | [525044] | |
LC-350189 | Drug Info | Phase 1 | Gout | [523497] | |
BOF-4272 | Drug Info | Discontinued in Phase 2 | Gout | [545270] | |
Y-700 | Drug Info | Discontinued in Phase 2 | Gout | [546844] | |
Inhibitor | 1,2,3,4,6-penta-O-galloyl-beta-D-glucose | Drug Info | [551350] | ||
1-(3-Cyano-phenyl)-1H-pyrazole-4-carboxylic acid | Drug Info | [526021] | |||
2-chloro-6(methylamino)purine | Drug Info | [528751] | |||
3,4'-(1H-1,2,4-triazole-3,5-diyl)dipyridine | Drug Info | [530410] | |||
3,5-bis(2-methylpyridin-4-yl)-1H-1,2,4-triazole | Drug Info | [530410] | |||
3,5-di(pyridin-4-yl)-1H-1,2,4-triazole | Drug Info | [530410] | |||
3-O-METHYLQUERCETIN | Drug Info | [551348] | |||
ACACETIN | Drug Info | [551348] | |||
Allopurinol | Drug Info | [535076], [537771], [538067] | |||
AMENTOFLAVONE | Drug Info | [551348] | |||
Aom-0763 | Drug Info | [543677] | |||
BAICALEIN | Drug Info | [551348] | |||
BOF-4272 | Drug Info | [526237], [551871] | |||
CHRYSOERIOL | Drug Info | [551348] | |||
Curcumin | Drug Info | [530090] | |||
DIHYDROKAEMPFEROL | Drug Info | [551348] | |||
Dioxothiomolybdenum(VI) ion | Drug Info | [551391] | |||
Febuxostat | Drug Info | [530677], [551717] | |||
Flavin-Adenine Dinucleotide | Drug Info | [551393] | |||
FUKUGETIN | Drug Info | [551348] | |||
LC-350189 | Drug Info | [533318] | |||
LIQUIRTIGENIN | Drug Info | [551348] | |||
NC-2500 | Drug Info | [543677] | |||
Oxypurinol | Drug Info | [533356] | |||
PERSICARIN | Drug Info | [551348] | |||
ROBINETIN | Drug Info | [551348] | |||
SCUTELLAREIN | Drug Info | [551348] | |||
Topiroxostat | Drug Info | [532545] | |||
WOGONIN | Drug Info | [551348] | |||
Y-700 | Drug Info | [551374] | |||
Cofactor | Cyclic pyranopterin monophosphate | Drug Info | [530850] | ||
Pathways | |||||
BioCyc Pathway | Purine nucleotides degradation | ||||
Urate biosynthesis/inosine 5' | |||||
-phosphate degradation | |||||
Guanosine nucleotides degradation | |||||
Adenosine nucleotides degradation | |||||
Retinoate biosynthesis II | |||||
KEGG Pathway | Purine metabolism | ||||
Caffeine metabolism | |||||
Drug metabolism - other enzymes | |||||
Metabolic pathways | |||||
Peroxisome | |||||
PANTHER Pathway | Adenine and hypoxanthine salvage pathway | ||||
Purine metabolism | |||||
PathWhiz Pathway | Caffeine Metabolism | ||||
Purine Metabolism | |||||
Reactome | Purine catabolism | ||||
WikiPathways | Oxidative Stress | ||||
Effects of Nitric Oxide | |||||
Metabolism of nucleotides | |||||
Selenium Micronutrient Network | |||||
References | |||||
Ref 521563 | ClinicalTrials.gov (NCT00063687) Oxypurinol Compared With Placebo for Class III-IV NYHA Congestive Heart Failure. U.S. National Institutes of Health. | ||||
Ref 523497 | ClinicalTrials.gov (NCT01361646) Safety, Tolerability and Pharmacokinetic/Pharmacodynamic Characteristics of LC350189. U.S. National Institutes of Health. | ||||
Ref 524617 | ClinicalTrials.gov (NCT02047461) Safety & Efficacy Study of ALXN1101 in Pediatric Patients With MoCD Type A Currently Treated With rcPMP. U.S. National Institutes of Health. | ||||
Ref 525044 | ClinicalTrials.gov (NCT02327754) Effect of Topiroxostat on Urinary Albumin Excretion Early Stage Diabetic Nephropathy and Hyperuricemia With or Without Gout. U.S. National Institutes of Health. | ||||
Ref 532348 | Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68. | ||||
Ref 538511 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018659. | ||||
Ref 541876 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6795). | ||||
Ref 541899 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6817). | ||||
Ref 542031 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7000). | ||||
Ref 526021 | Bioorg Med Chem Lett. 2001 Apr 9;11(7):879-82.Synthesis and structure-activity relationships of 1-phenylpyrazoles as xanthine oxidase inhibitors. | ||||
Ref 526237 | Enantioselective uptake of BOF-4272, a xanthine oxidase inhibitor with a chiral sulfoxide, by isolated rat hepatocytes. Yakugaku Zasshi. 2001 Dec;121(12):989-94. | ||||
Ref 528751 | Bioorg Med Chem. 2007 May 15;15(10):3450-6. Epub 2007 Mar 12.The screening and characterization of 6-aminopurine-based xanthine oxidase inhibitors. | ||||
Ref 530090 | J Nat Prod. 2009 Apr;72(4):725-31.Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. | ||||
Ref 530410 | Bioorg Med Chem Lett. 2009 Nov 1;19(21):6225-9. Epub 2009 Sep 2.Discovery of 3-(2-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole, FYX-051 - a xanthine oxidoreductase inhibitor for the treatment of hyperuricemia [corrected]. | ||||
Ref 530850 | Successful treatment of molybdenum cofactor deficiency type A with cPMP. Pediatrics. 2010 May;125(5):e1249-54. | ||||
Ref 532545 | QT/QTc study conducted in Japanese adult healthy subjects: a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation. J Clin Pharmacol. 2014 Apr;54(4):446-52. | ||||
Ref 533318 | Pharmacokinetics, pharmacodynamics, and tolerability of LC350189, a novel xanthine oxidase inhibitor, in healthy subjects. Drug Des Devel Ther. 2015 Aug 31;9:5033-49. | ||||
Ref 533356 | Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol. 1988 Jan 15;37(2):349-52. | ||||
Ref 535076 | Purification, crystallization and preliminary X-ray diffraction studies of xanthine dehydrogenase and xanthine oxidase isolated from bovine milk. Acta Crystallogr D Biol Crystallogr. 2000 Dec;56(Pt 12):1656-8. | ||||
Ref 538067 | Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle. Microsurgery. 1996;17(9):517-23. | ||||
Ref 543677 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2646). | ||||
Ref 551348 | Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod. 1988 Mar-Apr;51(2):345-8. | ||||
Ref 551350 | Pentagalloylglucose, a xanthine oxidase inhibitor from a Paraguayan crude drug, "Molle-i" (Schinus terebinthifolius). J Nat Prod. 1989 Jan-Feb;52(1):210-1. |
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