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xanthine dehydrogenase

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Target not currently curated in GtoImmuPdb

Target id: 2646

Nomenclature: xanthine dehydrogenase

Abbreviated Name: XDH

Family: Nucleoside synthesis and metabolism, 1.-.-.- Oxidoreductases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1333 2p23.1 XDH xanthine dehydrogenase
Mouse - 1335 17 45.25 cM Xdh xanthine dehydrogenase
Rat - 1331 6q13-q14 Xdh xanthine dehydrogenase
Previous and Unofficial Names Click here for help
xanthine dehydrogenase/oxidase | xanthine oxidase | XO | XOR
Database Links Click here for help
Alphafold P47989 (Hs), Q00519 (Mm), P22985 (Rn)
BRENDA 1.17.1.4
CATH/Gene3D 1.10.150.120, 3.10.20.30, 3.30.365.10, 3.30.43.10, 3.30.465.10, 3.90.1170.50
ChEMBL Target CHEMBL1929 (Hs), CHEMBL1075246 (Rn)
DrugBank Target P47989 (Hs)
Ensembl Gene ENSG00000158125 (Hs), ENSMUSG00000024066 (Mm), ENSRNOG00000007081 (Rn)
Entrez Gene 7498 (Hs), 22436 (Mm), 497811 (Rn)
Human Protein Atlas ENSG00000158125 (Hs)
KEGG Enzyme 1.17.1.4
KEGG Gene hsa:7498 (Hs), mmu:22436 (Mm), rno:497811 (Rn)
OMIM 607633 (Hs)
Orphanet ORPHA120558 (Hs)
Pharos P47989 (Hs)
RefSeq Nucleotide NM_000379 (Hs), NM_011723 (Mm), NM_017154 (Rn)
RefSeq Protein NP_000370 (Hs), NP_035853 (Mm), NP_058850 (Rn)
UniProtKB P47989 (Hs), Q00519 (Mm), P22985 (Rn)
Wikipedia XDH (Hs)
Enzyme Reaction Click here for help
EC Number: 1.17.1.4

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
febuxostat Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Bt Inhibition 9.9 pKi 6
⤷ pKi 9.9 (Ki 1.2x10-10 M) [6]
Description: In vitro assay using purified bovine enzyme
allopurinol Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 5.2 pKi 1
⤷ pKi 5.2 (Ki 7x10-6 M) [1]
febuxostat Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 8.9 pIC50 2
⤷ pIC50 8.9 (IC50 1.26x10-9 M) [2]
Description: Inhibition of baculovirus expressed C-terminally FLAG-tagged human xanthine oxidase (aa 1-1333).
WN1703 Small molecule or natural product Immunopharmacology Ligand Bt Inhibition 8.2 pIC50 5
⤷ pIC50 8.2 (IC50 5.7x10-9 M) [5]
Description: Inhibition of XHD in cow's milk
febuxostat Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Bt Inhibition 7.5 pIC50 4
⤷ pIC50 7.5 (IC50 3x10-8 M) [4]
Description: In vitro assay using purified bovine enzyme
allopurinol Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 5.4 pIC50 1
⤷ pIC50 5.4 (IC50 4.2x10-6 M) [1]
topiroxostat Small molecule or natural product Ligand has a PDB structure N/A Inhibition - -
⤷
View species-specific inhibitor tables
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Xanthinuria type I
OMIM: 278300
Orphanet: ORPHA93601
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Nonsense Human R228X 682C>T This nucleotide transition causes a Arg to Ter (termination) nonsense substitution at codon 228 resulting in a truncated protein. 3

References

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1. Biagi G, Costantini A, Costantino L, Giorgi I, Livi O, Pecorari P, Rinaldi M, Scartoni V. (1996) Synthesis and biological evaluation of new imidazole, pyrimidine, and purine derivatives and analogs as inhibitors of xanthine oxidase. J Med Chem, 39 (13): 2529-35. [PMID:8691450]

2. Evenäs J, Edfeldt F, Lepistö M, Svitacheva N, Synnergren A, Lundquist B, Gränse M, Rönnholm A, Varga M, Wright J et al.. (2014) HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase. Bioorg Med Chem Lett, 24 (5): 1315-21. [PMID:24508129]

3. Ichida K, Amaya Y, Kamatani N, Nishino T, Hosoya T, Sakai O. (1997) Identification of two mutations in human xanthine dehydrogenase gene responsible for classical type I xanthinuria. J Clin Invest, 99 (10): 2391-7. [PMID:9153281]

4. Khanna S, Burudkar S, Bajaj K, Shah P, Keche A, Ghosh U, Desai A, Srivastava A, Kulkarni-Almeida A, Deshmukh NJ et al.. (2012) Isocytosine-based inhibitors of xanthine oxidase: design, synthesis, SAR, PK and in vivo efficacy in rat model of hyperuricemia. Bioorg Med Chem Lett, 22 (24): 7543-6. [PMID:23122864]

5. Li J, Wu F, Liu X, Zou Y, Chen H, Li Z, Zhang L. (2017) Synthesis and bioevaluation of 1-phenyl-pyrazole-4-carboxylic acid derivatives as potent xanthine oxidoreductase inhibitors. Eur J Med Chem, 140: 20-30. [PMID:28918097]

6. Okamoto K, Eger BT, Nishino T, Kondo S, Pai EF, Nishino T. (2003) An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibition. J Biol Chem, 278 (3): 1848-55. [PMID:12421831]

How to cite this page

1.-.-.- Oxidoreductases: xanthine dehydrogenase. Last modified on 23/07/2024. Accessed on 13/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2646.