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Protein / target

Melatonin receptor type 1A

Encoded byMTNR1AP48039Homo 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

G protein-coupled receptor

Primary biology

GPCR signalling

Strongest disease association

Sleep Initiation and Maintenance Disorders

Via encoding gene MTNR1A · Clinical 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

High affinity receptor for melatonin.

View complete UniProt function annotation

High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity. Possibly involved in sleep induction, by melatonin activation of the potassium channel KCNMA1/BK and the dissociation of G-beta and G-gamma subunits, thereby decreasing synaptic transmission (By similarity)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (9)

Gene Ontology

  • Cplasma membrane
  • Creceptor complex
  • FG protein-coupled receptor activity
  • Fhormone binding
  • Fmelatonin receptor activity
  • Padenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
  • Pcircadian rhythm
  • PG protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
  • Pmating behavior

350 aa · 39 kDa

Biological roles

Reactome v97

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

Synaptic signallingUniProtG protein-coupled signallingGO
View supporting evidence

Synaptic signalling

  • ·High affinity receptor for melatonin. Likely to mediate the reproductive and circadian a…

G protein-coupled signalling

  • ·G protein-coupled receptor activity
  • ·adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
  • ·G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messen…
View underlying pathways (2)

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

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

GNB1GNAI1GPR50MTNR1BGNG2FAT1GNAI2GNAI3FAT3GNB4MTNR1A

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

3 medicines · 5 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.

Autistic Disorder1 medicine
Depressive Disorder1 medicine
Sleep Disorders, Circadian Rhythm1 medicine
Sleep Initiation and Maintenance Disorders1 medicine
Sleep Wake Disorders1 medicine

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

3

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.

Melatonin
ApprovedAgonist

Melatonin receptor agonist

Indicated for Autistic Disorder, Sleep Initiation and Maintenance Disorders

Acts on a complex — shared with MTNR1B · 1 of 2 recorded protein targets — narrow recorded profile

agomelatine
ApprovedAgonist

Melatonin receptor agonist

Indicated for Depressive Disorder

Acts on a complex — shared with MTNR1B · 1 of 3 recorded protein targets — narrow recorded profile

tasimelteon
ApprovedAgonist

Melatonin receptor agonist

Indicated for Sleep Disorders, Circadian Rhythm, Sleep Wake Disorders

Acts on a complex — shared with MTNR1B · 1 of 2 recorded protein targets — narrow recorded profile

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 MTNR1A

Gene-level evidence surfaced through the gene MTNR1Athat 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.

Sleep Initiation and Maintenance Disorders
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Major depressive disorder
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.58

Sleep disorder
0.48Limited support

Clinical evidence dominant · Open Targets 0.39

Sleep Disorders, Circadian Rhythm
0.48Limited support

Clinical evidence dominant · Open Targets 0.39

Autistic Disorder
0.48Limited support

Clinical evidence dominant · Open Targets 0.39

View evidence synthesis (5)
Sleep Initiation and Maintenance DisordersModerately supported
0.74
agreement 0.590.90
Clinical97%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

Major depressive disorderModerately supported
0.72
agreement 0.560.87
Clinical97%Literature3%

Open Targets aggregate 0.58 · 2 independent evidence families

Sleep disorderLimited support
0.48
agreement 0.330.64
Clinical97%Literature3%

Open Targets aggregate 0.39 · 2 independent evidence families

Sleep Disorders, Circadian RhythmLimited support
0.48
agreement 0.330.64
Clinical99%Literature1%

Open Targets aggregate 0.39 · 2 independent evidence families

Autistic DisorderLimited support
0.48
agreement 0.330.64
Clinical99%Literature1%

Open Targets aggregate 0.39 · 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
Sleep Initiation and Maintenance Disorders0.60
Major depressive disorder0.58
Sleep Disorders, Circadian Rhythm0.39
Autistic Disorder0.39
Sleep disorder0.39
Neurodegenerative Diseases0.36

Drug development

5 compounds recorded · 4 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 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (5)
MELATONINApproval
AGOMELATINEApproval
PIROMELATINEPhase 2 3
TASIMELTEONApproval
RAMELTEONApproval

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 (go cc high conf and uniprot loc 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 · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

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)

RECRUITING · via Melatonin · NCT05502900

ACTIVE_NOT_RECRUITING · via Melatonin · NCT07305350

RECRUITING · via Melatonin · NCT06226025

ACTIVE_NOT_RECRUITING · via Melatonin · NCT00262470

NOT_YET_RECRUITING · via Melatonin · NCT07334197

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 3 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. Supplemental approval2026-07-27

    Supplemental approval: TASIMELTEON (NDA205677)

    fda · regulatory · fda · via tasimelteon

  2. Trial status changed2026-07-27

    A Multicenter, Double-blind, Randomized Study to Evaluate the Effects of Tasimelteon vs. Placebo in Participants With Delayed Sleep-Wake Phase Disorder (DSWPD)

    Status changed to Active, not recruiting · ClinicalTrials.gov · via tasimelteon

  3. Trial status changed2026-07-14

    The Effect of Preoperative Oral Melatonin on Postoperative Pain Control After Cesarean Section: A Dose Comparison Study

    Status changed to Completed · ClinicalTrials.gov · via Melatonin

  4. New publication2025-04-23
    Molecular Links Between Circadian Rhythm Disruption, Melatonin, and Neurodegenerative Diseases: An Updated Review.

    Molecules (Basel, Switzerland) · 2025 · 12 citations · Europe PMC · via Melatonin

  5. New publication2024-09-03
    Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment.

    Ageing research reviews · 2024 · 37 citations · Europe PMC · via Melatonin

  6. New publication2024-07-13
    The Role of Gut Microbiome in Sleep Quality and Health: Dietary Strategies for Microbiota Support.

    Nutrients · 2024 · 31 citations · Europe PMC · via Melatonin

  7. New publication2024-06-28
    Presence of melatonin in foods of daily consumption: The benefit of this hormone for health.

    Food chemistry · 2024 · 7 citations · Europe PMC · via Melatonin

  8. Regulatory approval2022-11-07

    Approval: Melatonin Neurim (EMA)

    ema · regulatory · ema · via Melatonin

  9. Regulatory approval2015-07-03

    Approval: Hetlioz (EMA)

    ema · regulatory · ema · via tasimelteon

  10. Safety communication2014-12-11

    Drug Safety Update: Agomelatine (Valdoxan): risk of liver toxicity

    mhra · safety · mhra · via agomelatine

  11. Safety communication2014-12-11

    Drug Safety Update: Agomelatine (Valdoxan/ Thymanax): risk of dose-related hepatotoxicity and liver failure

    mhra · safety · mhra · via agomelatine

  12. Regulatory approval2007-06-29

    Approval: Circadin (EMA)

    ema · regulatory · ema · via Melatonin

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.