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Protein / target

Catechol O-methyltransferase

Encoded byCOMTP21964Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Catechol O-methyltransferase

Strongest disease association

Hair color

Via encoding gene COMT · Genetic evidence · score 0.80

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

2 papers · latest 2024

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

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones.

View complete UniProt function annotation

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol

Subcellular location

CytoplasmCell membrane
Domains and Gene Ontology detail (17)

Gene Ontology

  • Caxon
  • Ccytosol
  • Cdendrite
  • Cendoplasmic reticulum
  • Cextracellular exosome
  • Cmembrane
  • Cplasma membrane
  • Fcatechol O-methyltransferase activity
  • Fmagnesium ion binding
  • Fmethyltransferase activity
  • FO-methyltransferase activity
  • Pcatecholamine catabolic process

271 aa · 30 kDa · 2 isoforms

Biological roles

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

Lipid & lipoprotein metabolismGO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·lipid metabolic process

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

Approved medicines with mapped indications

2 medicines · 2 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.

Parkinson's Disease2 medicines
Liver Failure1 medicine

3 medicines meet Open Targets' target-level approved-medicine definition; the 2 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

2

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.

entacapone
Narrow target profileApprovedInhibitor

Catechol O-methyltransferase inhibitor

Indicated for Parkinson's Disease

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

tolcapone
Narrow target profileApprovedInhibitor

Catechol O-methyltransferase inhibitor

Indicated for Liver Failure, Parkinson's Disease

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 COMT

Gene-level evidence surfaced through the gene COMTthat 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.

Hair color
0.80Well supported

Genetic evidence dominant · Open Targets 0.48

Parkinson's Disease
0.78Well supported

Clinical evidence dominant · Open Targets 0.63

Diabetes Mellitus, Type 2
0.62Moderately supported

Genetic evidence dominant · Open Targets 0.37

Bardet-Biedl Syndrome
0.56Moderately supported

Genetic evidence dominant · Open Targets 0.34

Schizophrenia
0.42Limited support

Genetic evidence dominant · Open Targets 0.24

View evidence synthesis (5)
Hair colorWell supported
0.80
agreement 0.680.92
Genetic100%

Open Targets aggregate 0.48 · 1 independent evidence family

Parkinson's DiseaseWell supported
0.78
agreement 0.620.93
Clinical84%Literature16%

Open Targets aggregate 0.63 · 2 independent evidence families

Diabetes Mellitus, Type 2Moderately supported
0.62
agreement 0.480.76
Genetic88%Literature12%

Open Targets aggregate 0.37 · 2 independent evidence families

Bardet-Biedl SyndromeModerately supported
0.56
agreement 0.440.68
Genetic100%

Open Targets aggregate 0.34 · 1 independent evidence family

SchizophreniaLimited support
0.42
agreement 0.320.53
Genetic49%Literature28%Clinical23%Genetic literaturedup

Open Targets aggregate 0.24 · 3 independent evidence families · 1 not counted as duplicate

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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
Parkinson's Disease0.63
Hair color0.48
Diabetes Mellitus, Type 20.37
Bardet-Biedl Syndrome0.34
Restless Legs Syndrome0.26
Schizophrenia0.24

Drug development

4 compounds recorded · 3 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (4)
NEBICAPONEPhase 2
TOLCAPONEApproval
OPICAPONEApproval
ENTACAPONEApproval

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 high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (11)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

require medication to treat neonatal abstinence syndromeClinPGxtardive dyskinesiaClinPGxvomitingClinPGxhyperalgesiaClinPGxmore adverse eventsClinPGxblood pressureClinPGxextrapyramidal symptomsClinPGxerythemaClinPGxa loss of libidoClinPGxneonatal abstinence syndromeClinPGxdizzinessClinPGxnephrotoxicityClinPGx

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)

COMPLETED · via tolcapone · NCT01001520

COMPLETED · via tolcapone · NCT00927563

COMPLETED · via tolcapone · NCT00604591

COMPLETED · via tolcapone · NCT04205994

COMPLETED · via tolcapone · NCT02260570

ClinicalTrials.gov via the drug-target graph.

What's happening now

6

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target 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. New publication2020-07-02
    The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder.

    Psychopharmacology · 2020 · 12 citations · Europe PMC · via tolcapone

  2. New publication2016-12-20
    Right inferior frontal cortex activity correlates with tolcapone responsivity in problem and pathological gamblers.

    NeuroImage. Clinical · 2017 · 13 citations · Europe PMC · via tolcapone

  3. Regulatory approval2011-08-18

    Approval: Entacapone Orion (EMA)

    ema · regulatory · ema · via entacapone

  4. Regulatory approval1998-09-22

    Approval: Comtan (EMA)

    ema · regulatory · ema · via entacapone

  5. Regulatory approval1998-09-16

    Approval: Comtess (EMA)

    ema · regulatory · ema · via entacapone

  6. Regulatory approval1997-08-27

    Approval: Tasmar (EMA)

    ema · regulatory · ema · via tolcapone

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.

Research activity

2 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Frank MJ · Proceedings of the National Academy of Sciences of the United States of America · 2007

Koyama E · Translational psychiatry · 2024

Recent

Genetics of child aggression, a systematic review.

Koyama E · Translational psychiatry · 2024

Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning.

Frank MJ · Proceedings of the National Academy of Sciences of the United States of America · 2007

Europe PMC papers linked directly to this protein.