Small-molecule drugs to boost orexin for better sleep and memory
Identification of small molecule orexin agonists
This project searches for new small-molecule drugs that activate orexin receptors to help people with sleep problems and memory decline linked to aging and Alzheimer’s.
Quick facts
| Grant type | R03 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Research Triangle Institute NIH-funded |
| Lab location | 1 site (Research Triangle Park, United States) |
| Project ID | NIH-11302634 on NIH RePORTER |
What this research studies
Researchers will screen about 100,000 compounds in the lab to find small molecules that activate the orexin receptors OX1R and OX2R. The team uses high-throughput laboratory tests to spot compounds that bind and turn on these receptors, then follows up with more detailed lab and animal tests to check effects on wakefulness and memory. Previous compounds from this group (ROXA-43 and ROXA-47) improved wakefulness and memory in mice without signs of reward-related side effects, which motivates this search for additional candidates. This work is done in the lab and in animal models now and could lead to drug candidates that later move into human testing.
Who could benefit from this research
Good fit: Ideal candidates for future clinical trials would be people with orexin deficiency such as narcolepsy or patients with Alzheimer’s disease or age-related sleep and memory problems.
Not a fit: People whose sleep or memory problems stem from causes unrelated to orexin signaling, or who cannot tolerate central nervous system stimulants, may not benefit from this approach.
Why it matters
Potential benefit: If successful, this work could produce an orally usable drug that restores orexin signaling and improves sleep, daytime alertness, and memory in people with narcolepsy, age-related sleep loss, or Alzheimer’s disease.
How similar studies have performed: Animal studies and early lab work with the team’s ROXA compounds showed improved wakefulness and memory in mice, but no small-molecule orexin agonist has yet reached human clinical approval.
Where this research is happening
Research Triangle Park, United States
- Research Triangle Institute — Research Triangle Park, United States (Active)
Researchers
- Principal investigator: Zhang, Yanan — Research Triangle Institute
- Study coordinator: Zhang, Yanan
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.