HCRTR1

Hypocretin Receptor 1

Score: 0.602 Price: $0.60 Medium Druggability Status: active Wiki: HCRTR1

🧠 Neurodegeneration

HYPOTHESES

3

PAPERS

26

KG EDGES

60

DEBATES

1

3D Protein Structure

🧬 HCRTR1 — PDB 4ZJ8 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.60

Clinical Stage

Approved

Target Class

Gpcr

Safety

0.70

Druggability Analysis

Drug Development0.60

Structural Tractability0.85

Target Class0.85

Safety Profile0.70

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 —

4ZJ8 4ZJC 6TO7 6TOD 6TOS+9 more

UniProt: A6NMV7

🧬 3D Protein Structure

🧬 HCRTR1 — PDB 4ZJ8 Click to expand interactive 3D viewer

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

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.

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

8

Completed

0

Total Enrollment

493

By Phase

EARLY_PHASE1: 1 · PHASE2: 4 · PHASE4: 3

Efficacy of Suvorexant in the Treatment of Insomnia in Midlife Women With Pre-Diabetes Recruiting

PHASE4 NCT05593653 n=61

Insomnia, Diabetes, Menopause

Interventions: Suvorexant, Placebo

Sponsor: Brigham and Women's Hospital | Started: 2023-01-06

Effects of Lemborexant on Motor-sleep Comorbidity in Parkinson's Disease Recruiting

PHASE4 NCT07384429 n=44

Parkinson's Disease, Insomnia, Motor Disorder

Interventions: Lemborexant, placebo

Sponsor: YangPan | Started: 2026-03-19

Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial Recruiting

PHASE4 NCT06093126 n=1

Insomnia, Dementia, Frontotemporal Dementia

Interventions: Lemborexant 5 MG

Sponsor: Nova Scotia Health Authority | Started: 2023-12-11

Trial of Suvorexant for Sleep in Children With Autism Recruiting

PHASE2 NCT05546554 n=26

Autism, Autism Spectrum Disorder

Interventions: Suvorexant, Placebo

Sponsor: Stanford University | Started: 2023-08-09

Orexin Antagonism for Suicide Risk: A Proof-of-Concept Clinical Trial Recruiting

PHASE2 NCT06854224 n=30

Suicide Risk, Major Depressive Disorder (MDD)

Interventions: Suvorexant (dual orexin receptor antagon

Sponsor: Marianne Goodman | Started: 2025-09-01

DORA and LP in Alzheimer's Disease Biomarkers Recruiting

PHASE2 NCT06274528 n=201

Alzheimer Disease

Interventions: Lemborexant 10 mg, Lemborexant 20mg, Placebo

Sponsor: Washington University School of Medicine | Started: 2024-03-11

Effects of Lemborexant on Insomnia and Its Relationship to Mood and Behavior on Opioid Use Disorder Subjects Recruiting

PHASE2 NCT06981195 n=100

Opioid Use Disorder, Opioid Use, Insomnia

Interventions: Placebo, Lemborexant 10 MG

Sponsor: Virginia Commonwealth University | Started: 2025-05-27

Suvorexant and Alcohol Recruiting

EARLY_PHASE1 NCT06326684 n=30

Alcohol Use Disorder

Interventions: Alcohol, Placebo, Suvorexant

Sponsor: William Stoops | Started: 2024-06-07

Linked Hypotheses (0)

No linked hypotheses

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (3)

DRD2→HCRTR1HRH3→HCRTR1HCRTR2→HCRTR1

associated with (2)

HCRTR1→neurodegenerationHCRTR2→HCRTR1

co discussed (9)

AQP1→HCRTR1KCNK2→HCRTR1GJA1→HCRTR1HCRTR2→HCRTR1LOXL1-4→HCRTR1

▸ Show 4 more

HCRTR1→AQP4HCRTR1→LOXHCRTR1→SDC1HCRTR1→PDGFRB

interacts with (2)

HCRTR1→HCRTR2HCRTR2→HCRTR1

regulates (1)

HCRTR2→HCRTR1

therapeutic target (3)

HCRTR2→HCRTR1PNOC→HCRTR1TRPC6→HCRTR1

Debate History (1)

Should HCRTR1 (Hypocretin Receptor 1) be prioritized as a therapeutic target for2026-04-21