Druggability & Clinical Context
Druggability
Medium
Score: 0.60
Druggability Analysis
Structural Tractability0.85
Key Metrics
PDB Structures:
14
Known Drugs:
2
Approved:
0
In Clinical Trials:
0
Drug Pipeline (2 compounds)
Druggability Rationale: HCRTR1 is highly druggable due to its well-validated GPCR scaffold, extensive structural characterization (14 PDB structures with 2.11 Å resolution), and proven clinical precedent with two approved antagonists (Suvorexant, Lemborexant) demonstrating efficacy and safety. The high druggability score (0.90) reflects a defined orthosteric binding pocket amenable to small molecule optimization and favorable pharmacological tractability.
Mechanism: Small molecule antagonist blocking orexin receptor signaling
Drug Pipeline (2 compounds)
Known Drugs:Suvorexant (Approved) — Insomnia
Lemborexant (Approved) — Insomnia
Structural Data:PDB (14) ✓AlphaFold ✓Cryo-EM —
Selectivity & Safety Considerations
HCRTR1 selectivity versus HCRTR2 is critical to minimize potential off-target effects on appetite regulation and metabolic homeostasis; approved drugs like Suvorexant show dual antagonism, but isoform-selective agents are under investigation. Cross-reactivity with other GPCRs remains a consideration, though the orexin receptor family's distinct ligand binding profile provides inherent selectivity advantages.
Clinical Trials (8)
Relevant trials from ClinicalTrials.gov
By Phase
EARLY_PHASE1: 1 · PHASE2: 4 · PHASE4: 3
PHASE4
NCT05593653
n=61
Insomnia, Diabetes, Menopause
Interventions: Suvorexant, Placebo
Sponsor: Brigham and Women's Hospital | Started: 2023-01-06
PHASE4
NCT07384429
n=44
Parkinson's Disease, Insomnia, Motor Disorder
Interventions: Lemborexant, placebo
Sponsor: YangPan | Started: 2026-03-19
PHASE4
NCT06093126
n=1
Insomnia, Dementia, Frontotemporal Dementia
Interventions: Lemborexant 5 MG
Sponsor: Nova Scotia Health Authority | Started: 2023-12-11
PHASE2
NCT05546554
n=26
Autism, Autism Spectrum Disorder
Interventions: Suvorexant, Placebo
Sponsor: Stanford University | Started: 2023-08-09
PHASE2
NCT06854224
n=30
Suicide Risk, Major Depressive Disorder (MDD)
Interventions: Suvorexant (dual orexin receptor antagon
Sponsor: Marianne Goodman | Started: 2025-09-01
PHASE2
NCT06274528
n=201
Alzheimer Disease
Interventions: Lemborexant 10 mg, Lemborexant 20mg, Placebo
Sponsor: Washington University School of Medicine | Started: 2024-03-11
PHASE2
NCT06981195
n=100
Opioid Use Disorder, Opioid Use, Insomnia
Interventions: Placebo, Lemborexant 10 MG
Sponsor: Virginia Commonwealth University | Started: 2025-05-27
EARLY_PHASE1
NCT06326684
n=30
Alcohol Use Disorder
Interventions: Alcohol, Placebo, Suvorexant
Sponsor: William Stoops | Started: 2024-06-07