Summary
Dihexa is a small, orally active angiotensin IV analog developed at Washington State University. In rats it reversed memory deficits in several models and promoted new synapse formation by activating the hepatocyte growth factor (HGF)/c-Met system. It has never been tested in a published human trial.
Structure
A modified dipeptide (Tyr-Ile) capped with a hexanoyl group and an aminohexanoic amide, designed to cross the blood–brain barrier and resist breakdown.
How it works
Dihexa binds HGF and promotes its dimerization, enhancing c-Met receptor signalling, which drives dendritic spine growth and synaptogenesis in hippocampal neurons.
Research use cases
Areas where Dihexa has been studied. Inclusion here does not mean it works for that purpose.
- Cognitive deficit models (scopolamine, ageing)
- Synaptogenesis research
- Parkinson’s disease models
What the research found
Memory in rats
Orally and intraperitoneally administered dihexa improved spatial learning in scopolamine-treated and aged rats.1
HGF/c-Met dependence
The pro-cognitive and synapse-forming effects were blocked by c-Met antagonists, supporting HGF/c-Met as the mechanism.2
Safety and open questions
No human data. Because HGF/c-Met signalling drives growth in several cancers, researchers have raised a theoretical concern about long-term activation.
Regulatory status
Not approved. No published human trials. A related clinical candidate, fosgonimeton, failed its phase 2/3 Alzheimer’s trial in 2024.
Status was accurate when this page was last reviewed on October 26, 2026. Regulations change; check with the relevant authority before relying on it.
Dihexa: common questions
Is dihexa really more potent than BDNF?
That comparison comes from cell-culture assays of spine formation in the original research, not from studies in people. It should not be read as a clinical claim.
Is Dihexa approved for human use?
Not approved. No published human trials. A related clinical candidate, fosgonimeton, failed its phase 2/3 Alzheimer’s trial in 2024.
References
- McCoy AT, Benoist CC, Wright JW, et al. (2013). Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. Journal of Pharmacology and Experimental Therapeutics.
- Benoist CC, Kawas LH, Zhu M, et al. (2014). The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system. Journal of Pharmacology and Experimental Therapeutics.
Links open a PubMed search for the exact title, or the original source where one is given.