Druggability & Clinical Context
Druggability
High
Score: 0.90
Druggability Analysis
Structural Tractability0.70
Key Metrics
PDB Structures:
5
Known Drugs:
3
Approved:
3
In Clinical Trials:
0
Drug Pipeline (3 compounds)
3 Approved
Druggability Rationale: MTNR1B is highly druggable (0.90 score) due to its well-characterized GPCR architecture with multiple crystal structures available (5 PDB entries at 2.8ร
resolution), established chemical matter from three approved drugs, and proven G-protein coupling mechanism. The target's precedent with melatonin, ramelteon, and agomelatine demonstrates clear translational pathways from lead identification through clinical approval.
Mechanism: Small molecule agonists that activate G-protein coupled receptor signaling
Drug Pipeline (3 compounds)
3 Approved
Known Drugs:Melatonin (approved) โ sleep disorders
Ramelteon (approved) โ insomnia
Agomelatine (approved) โ depression
Structural Data:PDB (5) โAlphaFold โCryo-EM โ
Selectivity & Safety Considerations
MTNR1B selectivity versus the closely related MTNR1A isoform represents the primary selectivity challenge, as both receptors share high sequence homology and overlapping pharmacology; however, approved drugs demonstrate achievable selectivity profiles. Off-target binding to other GPCRs or melatonin pathway proteins requires careful evaluation to avoid unwanted circadian or hormonal effects.
Clinical Trials (8)
Relevant trials from ClinicalTrials.gov
By Phase
NA: 5 ยท PHASE1: 1 ยท PHASE2: 1 ยท Unknown: 1
NA
NCT00486551
n=26
Tourette Syndrome, Chronic Tic Disorder, Oppositional Defiant Disorder
Interventions: Anger control training
Sponsor: Yale University | Started: 2001-08
NA
NCT06909045
n=130
Deep Brain Stimulation, Parkinson Disease
Interventions: Adaptive DBS, Continue DBS
Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC | Started: 2026-01-27
PHASE1
NCT00843739
n=90
Parkinson's Disease
Interventions: EMST - Active Treatment, sham EMST
Sponsor: University of Florida | Started: 2004-01
Unknown
NCT03292575
n=441
Stroke
Interventions: Anticoagulants
Sponsor: Centre Hospitalier Universitaire Dijon | Started: 2016-01
NA
NCT01924312
n=80
Cerebrovascular Disease, Mild Cognitive Impairment
Interventions: Heart Health Intervention
Sponsor: Gregory Jicha, 323-5550 | Started: 2013-05
NA
NCT06306365
n=35
Executive Functions
Interventions: Modern board game-based learning
Sponsor: European University Miguel de Cervantes | Started: 2024-02-07
NA
NCT02260167
n=25
Alzheimer's Disease, Dementia
Interventions: A mix of natural treatments and medicati
Sponsor: Practitioners Alliance Network | Started: 2014-09
PHASE2
NCT03987295
n=33
Frontotemporal Dementia
Interventions: AL001
Sponsor: Alector Inc. | Started: 2019-09-27