What is dihexa?
Dihexa is a small synthetic compound built from angiotensin IV at Washington State University and studied in rat models of memory. It is often called a peptide; strictly it is a modified dipeptide. Its evidence base has thinned: key mechanism papers were retracted, and a close relative failed a phase 2/3 trial. Here is what is known and what is not.
Dihexa in one table.
| Chemical name | N-hexanoic-Tyr-Ile-(6) aminohexanoic amide |
|---|---|
| Core | Tyrosine and isoleucine, with an N-hexanoyl cap and a 6-aminohexanoic amide |
| Formula | C27H44N4O5 |
| Molecular weight | 504.7 g/mol |
| CAS number | 1401708-83-5 |
| PubChem CID | 129010512 |
| Other name | PNB-0408 |
| Status | No registered trials; not an approved drug |
Formula and mass from PubChem.
From angiotensin IV.
Dihexa came out of Joseph Harding and John Wright's group at Washington State University, which modified angiotensin IV, a fragment of the blood-pressure hormone angiotensin, to make it resist breakdown. A 2013 study evaluated these stabilized analogs in scopolamine-treated and aged rats and in hippocampal synapse-formation assays. That paper now carries an expression of concern.
Reported, not established.
The group describes dihexa as acting through hepatocyte growth factor (HGF) and its receptor c-Met, a system it reviewed as a target in Alzheimer's disease. But three of the group's key papers on that mechanism, from 2011, 2012 and 2014, have since been retracted, so the HGF account should be read as reported rather than established. An independent 2024 study in a rat model of Huntington's disease found no protective effect.
A relative in the clinic.
Athira Pharma took a phosphorylated relative of dihexa, fosgonimeton (ATH-1017), into a phase 2/3 trial in mild-to-moderate Alzheimer's disease, LIFT-AD. It did not meet its primary or secondary endpoints, and the open-label extension study was terminated as a result. Dihexa itself has no registered clinical trials.
Not approved.
Dihexa is not an approved drug. Dihexa acetate was nominated for pharmacy compounding and placed in Category 2, the FDA's group of bulk substances that may present significant safety risks; the nomination was later withdrawn, and the FDA list now shows it among withdrawn nominations, saying the agency has found no human exposure data and lacks important information on its safety. Helion supplies compounds for laboratory research use only.
Not supplied.
Helion does not supply dihexa. The research library covers the compounds it does supply, each with its own reference page and lab report.
Specs and storage by compound.
Questions (7)
What is dihexa?
A synthetic angiotensin IV analog, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, developed at Washington State University and studied in rat memory models.
Is dihexa a peptide?
Loosely. Its core is the dipeptide Tyr-Ile with chemical caps on both ends, so it is a modified dipeptide rather than a typical peptide.
How is dihexa thought to work?
Its developers describe it as acting through hepatocyte growth factor and c-Met, but key papers on that mechanism were retracted.
Were dihexa papers retracted?
Yes. Three of the developers' mechanism papers, from 2011, 2012 and 2014, were retracted, and the 2013 rat study carries an expression of concern.
What is fosgonimeton?
ATH-1017, a phosphorylated relative of dihexa. Its phase 2/3 Alzheimer's trial, LIFT-AD, did not meet its primary or secondary endpoints.
Has dihexa been tested in humans?
Dihexa itself has no registered clinical trials.
Does Helion sell dihexa?
No.
Published studies (4)
- Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents
- The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease
- Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats
- Fosgonimeton in mild-to-moderate Alzheimer's disease
Citations from PubMed for reference. They describe the compound in the literature, not any Helion lot, and nothing here is guidance on use.