MTNR1A

Melatonin receptor 1A

Score: 0.736 Price: $0.74 Medium Druggability Status: active Wiki: MTNR1A

🧠 Neurodegeneration

HYPOTHESES

2

PAPERS

48

KG EDGES

32

DEBATES

0

3D Protein Structure

🧬 MTNR1A — PDB 6ME3 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.57

Clinical Stage

Approved

Target Class

Gpcr

Safety

0.80

Druggability Analysis

Drug Development1.00

Structural Tractability0.70

Target Class0.85

Safety Profile0.80

Key Metrics

PDB Structures:

8

Known Drugs:

3

Approved:

3

In Clinical Trials:

0

Drug Pipeline (3 compounds)

3 Approved

Therapeutic Areas:

CNS/Neuroscience Cardiovascular Pain

Druggability Rationale: MTNR1A (Melatonin Receptor 1A) represents a promising druggable target with demonstrated small molecule tractability, evidenced by existing approved compounds like Ramelteon and structural resolution at 2.8Å. The receptor's high druggability score and multiple PDB structures suggest excellent potential for neurodegeneration therapeutic development, particularly given melatonin receptor modulators' established neural protective mechanisms.

Mechanism: Small molecule agonists that activate G-protein coupled receptor signaling

Drug Pipeline (3 compounds)

3 Approved

Known Drugs:

Melatonin (approved) — sleep disorders

Ramelteon (approved) — insomnia

Agomelatine (approved) — depression

Structural Data:

PDB (8) ✓AlphaFold ✓Cryo-EM ✓

6ME2 6ME3 6ME4 6ME5 6PS8+3 more

UniProt: Q8WZ72

Binding Pocket Analysis:

7TM binding cavity, extracellular loops

🧬 3D Protein Structure

🧬 MTNR1A — PDB 6ME3 Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

GPCR selectivity should be assessed against related receptor subtypes. Off-target GPCR activity (especially at hERG, muscarinic, and adrenergic receptors) is a common source of clinical adverse effects.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

3

Completed

5

Total Enrollment

1,597

By Phase

NA: 1 · PHASE2: 1 · PHASE3: 5 · PHASE4: 1

Affect of Melatonin on Sleep and Cognition in Cirrhosis Recruiting

NA NCT07046429 n=18

Hepatic Encephalopathy, Covert Hepatic Encephalopathy, Cirrhosis

Interventions: Melatonin tablet 3 mg once daily, Thiamine

Sponsor: Weill Medical College of Cornell University | Started: 2025-08-05

Switching Medication and Augmentation Strategies for SSRI-Resistant Adolescent Depression（SMART-I) Not Yet Recruiting

PHASE4 NCT07011693 n=400

Major Depressive Disorder (MDD)

Interventions: Sertraline, Agomelatine, Aripiprazole

Sponsor: Xinyu Zhou | Started: 2025-06-20

EFFICACY OF MELATONIN IN MANAGEMENT OF HYPOXIC ISCHEMIC ENCEPHALOPATHY (HIE) IN NEONATES Active Not Recruiting

PHASE2 NCT07305350 n=110

Hypoxic Ischaemic Encephalopathy (HIE)

Interventions: Melatonin, intravenous (IV) fluids, intensive monit

Sponsor: University of Child Health Sciences and Children's Hospital, | Started: 2025-12-10

The Role of Melatonin in the Effective Attainment of Sleep Electroencephalograms (EEG) in Children Completed

PHASE3 NCT02195661 n=194

Epilepsy, Electroencephalogram, Children

Interventions: Melatonin, Chloral Hydrate

Sponsor: University of Cape Town | Started: 2014-04

Long-Term Efficacy of Ramelteon on Endocrine Function in Adult Subjects With Chronic Insomnia Completed

PHASE3 NCT00656994 n=122

Insomnia

Interventions: Ramelteon, Placebo

Sponsor: Takeda | Started: 2003-01

Treatment of Insomnia in Elderly Sleep Apnea Patients With Ramelteon (TAK 375) Completed

PHASE3 NCT01048242 n=27

Insomnia, Obstructive Sleep Apnea

Interventions: rozerem, Placebo

Sponsor: University of Pennsylvania | Started: 2006-07

Safety and Efficacy of Ramelteon in Adults With Chronic Insomnia Completed

PHASE3 NCT00237497 n=275

Balance

Interventions: Ramelteon, Zopiclone, Placebo

Sponsor: Takeda | Started: 2005-07

Long-Term Efficacy and Safety of Ramelteon in Adults With Chronic Insomnia. Completed

PHASE3 NCT00247390 n=451

Chronic Insomnia

Interventions: Ramelteon, Placebo

Sponsor: Takeda | Started: 2005-07

Linked Hypotheses (1)

Circadian Glymphatic Rescue Therapy (Melatonin-focused)0.546

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

MTNR1A → neurodegeneration

co discussed (14)

MTNR1A → CX3CR1

MTNR1A → HCRT

MTNR1A → CACNA1G

MTNR1A → ADORA2A

MTNR1A → ADRA2A

...and 9 more

implicated in (1)

MTNR1A → neurodegeneration

interacts with (2)

MTNR1A → LRP1

MTNR1A → MTNR1B

participates in (2)

MTNR1A → LRP1 receptor-mediated transcytosis

MTNR1A → Circadian rhythm / glymphatic clearance

Debate History (0)

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