Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7RJY8)

DTT Name Xanthine dehydrogenase/oxidase (XDH)
Synonyms Xanthine oxidase; Xanthine dehydrogenase; XDHA
Gene Name XDH
DTT Type
Successful target
 [1]
Related Disease
Inborn purine/pyrimidine/nucleotide metabolism error [ICD-11: 5C55]
Mineral deficiency [ICD-11: 5B5K]
BioChemical Class
CH/CH(2) oxidoreductase
UniProt ID
XDH_HUMAN
TTD ID
T40954
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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
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.
KEGG Pathway
Purine metabolism (hsa00230 )
Caffeine metabolism (hsa00232 )
Drug metabolism - other enzymes (hsa00983 )
Metabolic pathways (hsa01100 )
Peroxisome (hsa04146 )
Reactome Pathway
Purine catabolism (R-HSA-74259 )
BioCyc Pathway
MetaCyc:HS08270-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
3 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Allopurinol DMLPAOB Hyperuricaemia 5C55.Y Approved [1], [2], [3]
Febuxostat DMDEXQ0 Hyperuricaemia 5C55.Y Approved [4], [5]
Fosdenopterin DMR0TYK Molybdenum cofactor deficiency 5B5K.A Approved [6]
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6 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Curcumin DMQPH29 Solid tumour/cancer 2A00-2F9Z Phase 3 [7]
Oxypurinol DMURH4X Heart failure BD10-BD13 Phase 2/3 [8]
BAICALEIN DM4C7E6 Influenza virus infection 1E30-1E32 Phase 2 [9]
TMX-049 DME8PFQ Diabetic nephropathy GB61.Z Phase 2 [10]
Topiroxostat DMA04DE Gout FA25 Phase 2 [11]
LC-350189 DMHT3CB Gout FA25 Phase 1 [12]
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⏷ Show the Full List of 6 Clinical Trial Drug(s)
35 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Azaindole derivative 3 DM2EDOM N. A. N. A. Patented [13]
Azaindole derivative 4 DMCKSJ8 N. A. N. A. Patented [13]
Azaindole derivative 5 DMD2BL3 N. A. N. A. Patented [13]
Azaindole derivative 6 DMJBGHL N. A. N. A. Patented [13]
Azaindole derivative 7 DMA2JGU N. A. N. A. Patented [13]
Azole benzene derivative 1 DM0E8YF N. A. N. A. Patented [13]
Azole benzene derivative 2 DMJG7M6 N. A. N. A. Patented [13]
Azole benzene derivative 3 DMH8Q4T N. A. N. A. Patented [13]
Azole benzene derivative 4 DMDPHT1 N. A. N. A. Patented [13]
Fused heterocyclic compound 1 DMVU9RG N. A. N. A. Patented [13]
Fused heterocyclic compound 10 DMALDZ6 N. A. N. A. Patented [13]
Fused heterocyclic compound 11 DMJC4UZ N. A. N. A. Patented [13]
Fused heterocyclic compound 2 DM361J8 N. A. N. A. Patented [13]
Fused heterocyclic compound 3 DM2QVHY N. A. N. A. Patented [13]
Fused heterocyclic compound 4 DMHTS5G N. A. N. A. Patented [13]
Fused heterocyclic compound 5 DM10CGB N. A. N. A. Patented [13]
Fused heterocyclic compound 6 DM9DC3U N. A. N. A. Patented [13]
Fused heterocyclic compound 7 DMGNWJD N. A. N. A. Patented [13]
Fused heterocyclic compound 8 DMO8JE7 N. A. N. A. Patented [13]
Fused heterocyclic compound 9 DM25IMA N. A. N. A. Patented [13]
PMID27841045-Compound-129 DME2IHD N. A. N. A. Patented [13]
PMID27841045-Compound-130 DM2AVEG N. A. N. A. Patented [13]
PMID27841045-Compound-131 DMIKTVL N. A. N. A. Patented [13]
PMID27841045-Compound-132 DMCQB93 N. A. N. A. Patented [13]
PMID27841045-Compound-133 DMXPO6T N. A. N. A. Patented [13]
PMID27841045-Compound-134 DMY3U7N N. A. N. A. Patented [13]
PMID27841045-Compound-135 DMVR9TJ N. A. N. A. Patented [13]
PMID27841045-Compound-136 DM0KR8E N. A. N. A. Patented [13]
PMID27841045-Compound-137 DML25WY N. A. N. A. Patented [13]
PMID27841045-Compound-143 DMR7MBY N. A. N. A. Patented [13]
PMID27841045-Compound-144 DMR43JE N. A. N. A. Patented [13]
PMID27841045-Compound-145 DMAJRP1 N. A. N. A. Patented [13]
PMID27841045-Compound-155 DM675SX N. A. N. A. Patented [13]
PMID27841045-Compound-156 DML4AVX N. A. N. A. Patented [13]
PMID27841045-Compound-157 DM7EXNI N. A. N. A. Patented [13]
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⏷ Show the Full List of 35 Patented Agent(s)
2 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
BOF-4272 DMK0PVC Gout FA25 Discontinued in Phase 2 [14], [15]
Y-700 DMHFTD0 Gout FA25 Discontinued in Phase 2 [16]
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21 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
1,2,3,4,6-penta-O-galloyl-beta-D-glucose DMTK650 Discovery agent N.A. Investigative [17]
1-(3-Cyano-phenyl)-1H-pyrazole-4-carboxylic acid DMVTCGP Discovery agent N.A. Investigative [18]
2-chloro-6(methylamino)purine DML0S8M Discovery agent N.A. Investigative [19]
3,4'-(1H-1,2,4-triazole-3,5-diyl)dipyridine DMQDKYI Discovery agent N.A. Investigative [20]
3,5-bis(2-methylpyridin-4-yl)-1H-1,2,4-triazole DMV859W Discovery agent N.A. Investigative [20]
3,5-di(pyridin-4-yl)-1H-1,2,4-triazole DM6CBTE Discovery agent N.A. Investigative [20]
3-O-METHYLQUERCETIN DMVIZ1S Discovery agent N.A. Investigative [9]
Acacetin DMQOB0X Discovery agent N.A. Investigative [9]
AMENTOFLAVONE DMLRNV2 Discovery agent N.A. Investigative [9]
Aom-0763 DML1PV3 Gout FA25 Investigative [21]
CHRYSOERIOL DM96ECL Discovery agent N.A. Investigative [9]
DIHYDROKAEMPFEROL DM73OTF Discovery agent N.A. Investigative [9]
Dioxothiomolybdenum(VI) ion DM93MAB Discovery agent N.A. Investigative [22]
Flavin-Adenine Dinucleotide DM5S4GK Discovery agent N.A. Investigative [23]
FUKUGETIN DMWF82O Discovery agent N.A. Investigative [9]
LIQUIRTIGENIN DM6YSG3 Discovery agent N.A. Investigative [9]
NC-2500 DM45MGZ Hyperuricaemia 5C55.Y Investigative [21]
PERSICARIN DM3RGPF Discovery agent N.A. Investigative [9]
ROBINETIN DMASOWP Discovery agent N.A. Investigative [9]
SCUTELLAREIN DMJD03I Discovery agent N.A. Investigative [9]
Wogonin DMGCF51 Discovery agent N.A. Investigative [9]
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⏷ Show the Full List of 21 Investigative Drug(s)

The Drug-Metabolizing Enzyme (DME) Role of This DTT

DTT DME Name Xanthine dehydrogenase/oxidase (XDH) DME Info
Gene Name XDH
1 Approved Drug(s) Metabolized by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Solid tumour/cancer 2A00-2F9Z Approved [24]
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1 Clinical Trial Drug(s) Metabolized by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Xanthine DMFBOQ7 Apnea MD11.0 Phase 1 [25]
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References

1 Allopurinol: xanthine oxidase inhibitor. Tex Med. 1966 Jan;62(1):100-1.
2 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.
3 Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle. Microsurgery. 1996;17(9):517-23.
4 Clinical pipeline report, company report or official report of Takeda (2009).
5 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
7 Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod. 2009 Apr;72(4):725-31.
8 Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol. 1988 Jan 15;37(2):349-52.
9 Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod. 1988 Mar-Apr;51(2):345-8.
10 Clinical pipeline report, company report or official report of Teijin Pharma.
11 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.
12 Pharmacokinetics, pharmacodynamics, and tolerability of LC350189, a novel xanthine oxidase inhibitor, in healthy subjects. Drug Des Devel Ther. 2015 Aug 31;9:5033-49.
13 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.
14 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.
15 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
16 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
17 Pentagalloylglucose, a xanthine oxidase inhibitor from a Paraguayan crude drug, "Molle-i" (Schinus terebinthifolius). J Nat Prod. 1989 Jan-Feb;52(1):210-1.
18 Synthesis and structure-activity relationships of 1-phenylpyrazoles as xanthine oxidase inhibitors. Bioorg Med Chem Lett. 2001 Apr 9;11(7):879-82.
19 The screening and characterization of 6-aminopurine-based xanthine oxidase inhibitors. Bioorg Med Chem. 2007 May 15;15(10):3450-6.
20 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.
21 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).
22 DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
23 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
24 Xanthine oxidoreductase in drug metabolism: beyond a role as a detoxifying enzyme. Curr Med Chem. 2016;23(35):4027-4036.
25 Molecular characterization and taurine regulation of two novel CDOs (CDO1 and CDO2) from Carassius auratus. Comp Biochem Physiol B Biochem Mol Biol. 2019 Sep;235:54-61.