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Protein / target

Xanthine dehydrogenase/oxidase

Encoded byXDHP47989Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
4
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Flavin adenine dinucleotide binding

Strongest disease association

Gout

Via encoding gene XDH · Genetic evidence · score 0.60

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Key enzyme in purine degradation.

View complete UniProt function annotation

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)

Subcellular location

CytoplasmPeroxisomeSecreted
Domains and Gene Ontology detail (30)

Domains & features

2Fe-2S ferredoxin-typeFAD-binding PCMH-type

Gene Ontology

  • Ccytosol
  • Cextracellular space
  • Cperoxisome
  • Csarcoplasmic reticulum
  • F2 iron, 2 sulfur cluster binding
  • FFAD binding
  • Fflavin adenine dinucleotide binding
  • Fhypoxanthine dehydrogenase activity
  • Fhypoxanthine oxidase activity
  • Firon ion binding
  • Fmolybdopterin cofactor binding
  • Fprotein homodimerization activity

1333 aa · 146 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Metabolic enzyme activityGO
View supporting evidence

Metabolic enzyme activity

  • ·hypoxanthine dehydrogenase activity
  • ·xanthine dehydrogenase activity
  • ·allantoin metabolic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

1 medicine · 3 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Arthritis, Gouty1 medicine
Gout1 medicine
Hyperuricemia1 medicine

4 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

febuxostat
Narrow target profileApprovedInhibitor

Xanthine dehydrogenase inhibitor

Indicated for Arthritis, Gouty, Gout, Hyperuricemia

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene XDH

Gene-level evidence surfaced through the gene XDH that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Gout
0.91Well supported

Clinical evidence dominant · Open Targets 0.70

Hyperuricemia
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.60

Leukemia
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Lymphoma
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Neoplasms
0.54Moderately supported

Clinical evidence dominant · Open Targets 0.41

View evidence synthesis (5)
GoutWell supported
0.91
agreement 0.801.00
Clinical52%Genetic42%Literature6%

Open Targets aggregate 0.70 · 3 independent evidence families

HyperuricemiaModerately supported
0.75
agreement 0.590.90
Clinical86%Literature14%

Open Targets aggregate 0.60 · 2 independent evidence families

LeukemiaModerately supported
0.74
agreement 0.590.90
Clinical99%Literature2%

Open Targets aggregate 0.60 · 2 independent evidence families

LymphomaModerately supported
0.74
agreement 0.590.90
Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

NeoplasmsModerately supported
0.54
agreement 0.380.69
Clinical81%Literature19%

Open Targets aggregate 0.41 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Gout0.70
Leukemia0.60
Hyperuricemia0.60
Lymphoma0.60
Neoplasms0.41

Drug development

6 compounds recorded · 4 approved · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (6)
TOPIROXOSTATApproval
BENDAZACApproval
ALLOPURINOL SODIUMPhase 3
FEBUXOSTATApproval
ALLOPURINOLApproval
OXYPURINOLPhase 2 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc med conf and go cc med conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc med confAB · GO CC med confPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

noncirrhotic portal hypertensionClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

UNKNOWN · via febuxostat · NCT04398251

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Safety communication2023-05-25

    Drug Safety Update: Febuxostat: updated advice for the treatment of patients with a history of major cardiovascular disease

    mhra · safety · mhra · via febuxostat

  2. Safety communication2019-07-17

    Drug Safety Update: Febuxostat (Adenuric): increased risk of cardiovascular death and all-cause mortality in clinical trial in patients with a history of major cardiovascular disease

    mhra · safety · mhra · via febuxostat

  3. Regulatory approval2019-03-28

    Approval: Febuxostat Krka (EMA)

    ema · regulatory · ema · via febuxostat

  4. New publication2018-03-12
    Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout.

    The New England journal of medicine · 2018 · 555 citations · Europe PMC · via febuxostat

  5. Regulatory approval2017-06-15

    Approval: Febuxostat Viatris (previously Febuxostat Mylan) (EMA)

    ema · regulatory · ema · via febuxostat

  6. Safety communication2014-12-11

    Drug Safety Update: Febuxostat (Adenuric▼): stop treatment if signs or symptoms of serious hypersensitivity

    mhra · safety · mhra · via febuxostat

  7. New publication2012-06-13
    Cardiovascular safety of febuxostat and allopurinol in patients with gout and cardiovascular comorbidities.

    American heart journal · 2012 · 38 citations · Europe PMC · via febuxostat

  8. New publication2010-12-01
    Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials.

    Clinical therapeutics · 2010 · 72 citations · Europe PMC · via febuxostat

  9. New publication2008-11-01
    Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial.

    Arthritis and rheumatism · 2008 · 402 citations · Europe PMC · via febuxostat

  10. New publication2008-06-01
    Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy.

    Nucleosides, nucleotides & nucleic acids · 2008 · 63 citations · Europe PMC · via febuxostat

  11. Regulatory approval2008-04-21

    Approval: Adenuric (EMA)

    ema · regulatory · ema · via febuxostat

  12. New publication2005-12-01
    Febuxostat compared with allopurinol in patients with hyperuricemia and gout.

    The New England journal of medicine · 2005 · 850 citations · Europe PMC · via febuxostat

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.