Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T40954
(Former ID: TTDS00056)
|
|||||
| Target Name |
Xanthine dehydrogenase/oxidase (XDH)
|
|||||
| Synonyms |
Xanthine oxidase; Xanthine dehydrogenase; XDHA
|
|||||
| Gene Name |
XDH
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Inborn purine/pyrimidine/nucleotide metabolism error [ICD-11: 5C55] | |||||
| 2 | Mineral deficiency [ICD-11: 5B5K] | |||||
| Function |
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). Key enzyme in purine degradation.
Click to Show/Hide
|
|||||
| BioChemical Class |
CH/CH(2) oxidoreductase
|
|||||
| UniProt ID | ||||||
| Sequence |
MTADKLVFFVNGRKVVEKNADPETTLLAYLRRKLGLSGTKLGCGEGGCGACTVMLSKYDR
LQNKIVHFSANACLAPICSLHHVAVTTVEGIGSTKTRLHPVQERIAKSHGSQCGFCTPGI VMSMYTLLRNQPEPTMEEIENAFQGNLCRCTGYRPILQGFRTFARDGGCCGGDGNNPNCC MNQKKDHSVSLSPSLFKPEEFTPLDPTQEPIFPPELLRLKDTPRKQLRFEGERVTWIQAS TLKELLDLKAQHPDAKLVVGNTEIGIEMKFKNMLFPMIVCPAWIPELNSVEHGPDGISFG AACPLSIVEKTLVDAVAKLPAQKTEVFRGVLEQLRWFAGKQVKSVASVGGNIITASPISD LNPVFMASGAKLTLVSRGTRRTVQMDHTFFPGYRKTLLSPEEILLSIEIPYSREGEYFSA FKQASRREDDIAKVTSGMRVLFKPGTTEVQELALCYGGMANRTISALKTTQRQLSKLWKE ELLQDVCAGLAEELHLPPDAPGGMVDFRCTLTLSFFFKFYLTVLQKLGQENLEDKCGKLD PTFASATLLFQKDPPADVQLFQEVPKGQSEEDMVGRPLPHLAADMQASGEAVYCDDIPRY ENELSLRLVTSTRAHAKIKSIDTSEAKKVPGFVCFISADDVPGSNITGICNDETVFAKDK VTCVGHIIGAVVADTPEHTQRAAQGVKITYEELPAIITIEDAIKNNSFYGPELKIEKGDL KKGFSEADNVVSGEIYIGGQEHFYLETHCTIAVPKGEAGEMELFVSTQNTMKTQSFVAKM LGVPANRIVVRVKRMGGGFGGKETRSTVVSTAVALAAYKTGRPVRCMLDRDEDMLITGGR HPFLARYKVGFMKTGTVVALEVDHFSNVGNTQDLSQSIMERALFHMDNCYKIPNIRGTGR LCKTNLPSNTAFRGFGGPQGMLIAECWMSEVAVTCGMPAEEVRRKNLYKEGDLTHFNQKL EGFTLPRCWEECLASSQYHARKSEVDKFNKENCWKKRGLCIIPTKFGISFTVPFLNQAGA LLHVYTDGSVLLTHGGTEMGQGLHTKMVQVASRALKIPTSKIYISETSTNTVPNTSPTAA SVSADLNGQAVYAACQTILKRLEPYKKKNPSGSWEDWVTAAYMDTVSLSATGFYRTPNLG YSFETNSGNPFHYFSYGVACSEVEIDCLTGDHKNLRTDIVMDVGSSLNPAIDIGQVEGAF VQGLGLFTLEELHYSPEGSLHTRGPSTYKIPAFGSIPIEFRVSLLRDCPNKKAIYASKAV GEPPLFLAASIFFAIKDAIRAARAQHTGNNVKELFRLDSPATPEKIRNACVDKFTTLCVT GVPENCKPWSVRV Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T87DEX | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Allopurinol | Drug Info | Approved | Hyperuricaemia | [2], [3] | |
| 2 | Febuxostat | Drug Info | Approved | Hyperuricaemia | [4], [5] | |
| 3 | Fosdenopterin | Drug Info | Approved | Molybdenum cofactor deficiency | [6] | |
| Clinical Trial Drug(s) | [+] 6 Clinical Trial Drugs | + | ||||
| 1 | Curcumin | Drug Info | Phase 3 | Solid tumour/cancer | [7], [8] | |
| 2 | Oxypurinol | Drug Info | Phase 2/3 | Heart failure | [9] | |
| 3 | BAICALEIN | Drug Info | Phase 2 | Influenza virus infection | [10] | |
| 4 | TMX-049 | Drug Info | Phase 2 | Diabetic nephropathy | [11] | |
| 5 | Topiroxostat | Drug Info | Phase 2 | Gout | [12] | |
| 6 | LC-350189 | Drug Info | Phase 1 | Gout | [13] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | BOF-4272 | Drug Info | Discontinued in Phase 2 | Gout | [14] | |
| 2 | Y-700 | Drug Info | Discontinued in Phase 2 | Gout | [15] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 66 Inhibitor drugs | + | ||||
| 1 | Allopurinol | Drug Info | [1], [16], [17] | |||
| 2 | Febuxostat | Drug Info | [18], [5] | |||
| 3 | Curcumin | Drug Info | [19] | |||
| 4 | Oxypurinol | Drug Info | [20] | |||
| 5 | BAICALEIN | Drug Info | [21] | |||
| 6 | TMX-049 | Drug Info | [22] | |||
| 7 | Topiroxostat | Drug Info | [23] | |||
| 8 | LC-350189 | Drug Info | [24] | |||
| 9 | Azaindole derivative 3 | Drug Info | [25] | |||
| 10 | Azaindole derivative 4 | Drug Info | [25] | |||
| 11 | Azaindole derivative 5 | Drug Info | [25] | |||
| 12 | Azaindole derivative 6 | Drug Info | [25] | |||
| 13 | Azaindole derivative 7 | Drug Info | [25] | |||
| 14 | Azole benzene derivative 1 | Drug Info | [25] | |||
| 15 | Azole benzene derivative 2 | Drug Info | [25] | |||
| 16 | Azole benzene derivative 3 | Drug Info | [25] | |||
| 17 | Azole benzene derivative 4 | Drug Info | [25] | |||
| 18 | Fused heterocyclic compound 1 | Drug Info | [25] | |||
| 19 | Fused heterocyclic compound 10 | Drug Info | [25] | |||
| 20 | Fused heterocyclic compound 11 | Drug Info | [25] | |||
| 21 | Fused heterocyclic compound 2 | Drug Info | [25] | |||
| 22 | Fused heterocyclic compound 3 | Drug Info | [25] | |||
| 23 | Fused heterocyclic compound 4 | Drug Info | [25] | |||
| 24 | Fused heterocyclic compound 5 | Drug Info | [25] | |||
| 25 | Fused heterocyclic compound 6 | Drug Info | [25] | |||
| 26 | Fused heterocyclic compound 7 | Drug Info | [25] | |||
| 27 | Fused heterocyclic compound 8 | Drug Info | [25] | |||
| 28 | Fused heterocyclic compound 9 | Drug Info | [25] | |||
| 29 | PMID27841045-Compound-129 | Drug Info | [25] | |||
| 30 | PMID27841045-Compound-130 | Drug Info | [25] | |||
| 31 | PMID27841045-Compound-131 | Drug Info | [25] | |||
| 32 | PMID27841045-Compound-132 | Drug Info | [25] | |||
| 33 | PMID27841045-Compound-133 | Drug Info | [25] | |||
| 34 | PMID27841045-Compound-134 | Drug Info | [25] | |||
| 35 | PMID27841045-Compound-135 | Drug Info | [25] | |||
| 36 | PMID27841045-Compound-136 | Drug Info | [25] | |||
| 37 | PMID27841045-Compound-137 | Drug Info | [25] | |||
| 38 | PMID27841045-Compound-143 | Drug Info | [25] | |||
| 39 | PMID27841045-Compound-144 | Drug Info | [25] | |||
| 40 | PMID27841045-Compound-145 | Drug Info | [25] | |||
| 41 | PMID27841045-Compound-155 | Drug Info | [25] | |||
| 42 | PMID27841045-Compound-156 | Drug Info | [25] | |||
| 43 | PMID27841045-Compound-157 | Drug Info | [25] | |||
| 44 | BOF-4272 | Drug Info | [26], [27] | |||
| 45 | Y-700 | Drug Info | [28] | |||
| 46 | 1,2,3,4,6-penta-O-galloyl-beta-D-glucose | Drug Info | [29] | |||
| 47 | 1-(3-Cyano-phenyl)-1H-pyrazole-4-carboxylic acid | Drug Info | [30] | |||
| 48 | 2-chloro-6(methylamino)purine | Drug Info | [31] | |||
| 49 | 3,4'-(1H-1,2,4-triazole-3,5-diyl)dipyridine | Drug Info | [32] | |||
| 50 | 3,5-bis(2-methylpyridin-4-yl)-1H-1,2,4-triazole | Drug Info | [32] | |||
| 51 | 3,5-di(pyridin-4-yl)-1H-1,2,4-triazole | Drug Info | [32] | |||
| 52 | 3-O-METHYLQUERCETIN | Drug Info | [21] | |||
| 53 | ACACETIN | Drug Info | [21] | |||
| 54 | AMENTOFLAVONE | Drug Info | [21] | |||
| 55 | Aom-0763 | Drug Info | [33] | |||
| 56 | CHRYSOERIOL | Drug Info | [21] | |||
| 57 | DIHYDROKAEMPFEROL | Drug Info | [21] | |||
| 58 | Dioxothiomolybdenum(VI) ion | Drug Info | [34] | |||
| 59 | Flavin-Adenine Dinucleotide | Drug Info | [35] | |||
| 60 | FUKUGETIN | Drug Info | [21] | |||
| 61 | LIQUIRTIGENIN | Drug Info | [21] | |||
| 62 | NC-2500 | Drug Info | [33] | |||
| 63 | PERSICARIN | Drug Info | [21] | |||
| 64 | ROBINETIN | Drug Info | [21] | |||
| 65 | SCUTELLAREIN | Drug Info | [21] | |||
| 66 | Wogonin | Drug Info | [21] | |||
| Cofactor | [+] 1 Cofactor drugs | + | ||||
| 1 | Fosdenopterin | Drug Info | [6] | |||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| BioCyc | [+] 5 BioCyc Pathways | + | ||||
| 1 | Purine nucleotides degradation | |||||
| 2 | Urate biosynthesis/inosine 5'-phosphate degradation | |||||
| 3 | Guanosine nucleotides degradation | |||||
| 4 | Adenosine nucleotides degradation | |||||
| 5 | Retinoate biosynthesis II | |||||
| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Purine metabolism | |||||
| 2 | Caffeine metabolism | |||||
| 3 | Drug metabolism - other enzymes | |||||
| 4 | Metabolic pathways | |||||
| 5 | Peroxisome | |||||
| Panther Pathway | [+] 2 Panther Pathways | + | ||||
| 1 | Adenine and hypoxanthine salvage pathway | |||||
| 2 | Purine metabolism | |||||
| Pathwhiz Pathway | [+] 2 Pathwhiz Pathways | + | ||||
| 1 | Caffeine Metabolism | |||||
| 2 | Purine Metabolism | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Purine catabolism | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Oxidative Stress | |||||
| 2 | Effects of Nitric Oxide | |||||
| 3 | Metabolism of nucleotides | |||||
| 4 | Selenium Micronutrient Network | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Allopurinol: xanthine oxidase inhibitor. Tex Med. 1966 Jan;62(1):100-1. | |||||
| REF 2 | URL: 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 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018659. | |||||
| REF 4 | URL: 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 5 | Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92. | |||||
| REF 6 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021 | |||||
| REF 7 | URL: 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 8 | Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68. | |||||
| REF 9 | ClinicalTrials.gov (NCT00063687) Oxypurinol Compared With Placebo for Class III-IV NYHA Congestive Heart Failure. U.S. National Institutes of Health. | |||||
| REF 10 | ClinicalTrials.gov (NCT03830684) A Randomized, Double-blind, Placebo-controlled, Multicenter and Phase IIa Clinical Trial for the Effectiveness and Safety of Baicalein Tablets in the Treatment of Improve Other Aspects of Healthy Adult With Influenza Fever. U.S. National Institutes of Health. | |||||
| REF 11 | ClinicalTrials.gov (NCT03449199) Phase 2 Study of TMX-049 in Subjects With Type 2 Diabetes and Albuminuria. U.S. National Institutes of Health. | |||||
| REF 12 | 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 13 | ClinicalTrials.gov (NCT01361646) Safety, Tolerability and Pharmacokinetic/Pharmacodynamic Characteristics of LC350189. U.S. National Institutes of Health. | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002649) | |||||
| REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010582) | |||||
| REF 16 | 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 17 | Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle. Microsurgery. 1996;17(9):517-23. | |||||
| REF 18 | Clinical pipeline report, company report or official report of Takeda (2009). | |||||
| REF 19 | Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod. 2009 Apr;72(4):725-31. | |||||
| REF 20 | Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol. 1988 Jan 15;37(2):349-52. | |||||
| REF 21 | Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod. 1988 Mar-Apr;51(2):345-8. | |||||
| REF 22 | Clinical pipeline report, company report or official report of Teijin Pharma. | |||||
| REF 23 | 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 24 | 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 25 | An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015).Expert Opin Ther Pat. 2017 Mar;27(3):311-345. | |||||
| REF 26 | 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 27 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 28 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 29 | Pentagalloylglucose, a xanthine oxidase inhibitor from a Paraguayan crude drug, "Molle-i" (Schinus terebinthifolius). J Nat Prod. 1989 Jan-Feb;52(1):210-1. | |||||
| REF 30 | Synthesis and structure-activity relationships of 1-phenylpyrazoles as xanthine oxidase inhibitors. Bioorg Med Chem Lett. 2001 Apr 9;11(7):879-82. | |||||
| REF 31 | The screening and characterization of 6-aminopurine-based xanthine oxidase inhibitors. Bioorg Med Chem. 2007 May 15;15(10):3450-6. | |||||
| REF 32 | 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 [... Bioorg Med Chem Lett. 2009 Nov 1;19(21):6225-9. | |||||
| REF 33 | URL: 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 34 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 35 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.