HCRTR2

Hypocretin Receptor 2

Score: 0.595 Price: $0.59 Medium Druggability Status: active Wiki: HCRTR2

🧠 Neurodegeneration

HYPOTHESES

3

PAPERS

57

KG EDGES

74

DEBATES

1

3D Protein Structure

🧬 HCRTR2 — PDB 7LS3 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:

11

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

Druggability Rationale: HCRTR2 exhibits exceptional druggability due to its well-characterized GPCR architecture, high-resolution crystal structures (1.96 Å), and validated clinical precedent with approved antagonists (Suvorexant, Lemborexant). The target's 0.90 druggability score reflects established ligand-binding capabilities and amenability to small-molecule optimization, with extensive structural biology support including 11 PDB structures and AlphaFold/cryo-EM data.

Mechanism: Small molecule antagonist blocking orexin receptor signaling

Drug Pipeline (2 compounds)

Known Drugs:

Suvorexant (Approved) — Insomnia

Lemborexant (Approved) — Insomnia

Structural Data:

PDB (11) ✓AlphaFold ✓Cryo-EM ✓

4S0V 5WQC 5WS3 6TPG 6TPJ+6 more

UniProt: S4WX84

🧬 3D Protein Structure

🧬 HCRTR2 — PDB 7LS3 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity between OX1R and OX2R isoforms is clinically relevant, as HCRTR2-selective antagonism may provide superior tolerability profiles compared to dual antagonists; however, cross-reactivity with related GPCRs and potential CNS off-target effects (e.g., monoamine receptors) require careful pharmacological profiling during lead optimization.

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

483

By Phase

PHASE2: 5 · PHASE4: 3

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

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

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

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

A Dual Orexin Receptor Antagonist to Reduce Biomarkers of Neurodegeneration in Adults With Insomnia. Recruiting

PHASE2 NCT06823752 n=20

Insomnia

Interventions: Lemborexant 10 MG, Placebo

Sponsor: Woolcock Institute of Medical Research | Started: 2025-05-13

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

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

Linked Hypotheses (1)

Orexin-Microglia Modulation Therapy0.707

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

HCRTR2→neurodegeneration

co discussed (17)

BMAL1→HCRTR2HCRTR2→CLOCKHCRTR2→BDNFHCRTR2→AQP4HCRTR2→MTNR1A

▸ Show 12 more

HCRTR2→CX3CR1HCRTR2→HCRTHCRTR2→CACNA1GHCRTR2→ADORA2AHCRTR2→ADRA2AAQP1→HCRTR2KCNK2→HCRTR2GJA1→HCRTR2HCRTR2→LOXL1-4HCRTR2→HCRTR1HCRTR2→LOXHCRTR2→SDC1

interacts with (2)

HCRTR1→HCRTR2HCRTR2→HCRTR1

Debate History (1)

Should HCRTR2 (Hypocretin Receptor 2) be prioritized as a therapeutic target for2026-04-21