Research Overview
Dihexa is a synthetic, metabolically stabilized oligopeptide analog derived from angiotensin IV (AngIV). It was engineered from the Nle-Tyr-Ile N-terminal core of Nle1-AngIV by N-hexanoylation and a C-terminal 6-aminohexanoic amide extension, modifications intended to raise lipophilicity and metabolic stability for use as a research tool compound. It is cataloged under several research designations, including PNB-0408 and ATH-1001, and is indexed in PubChem as CID 129010512.
In preclinical literature, Dihexa is described as a small-molecule potentiator of the hepatocyte growth factor (HGF) / c-Met receptor tyrosine kinase system, and it has been used as a research reagent across neuroscience, sensory-biology, and stem-cell differentiation studies. All reported activity described on this page is drawn from in-vitro and animal-model work. No human efficacy has been established.
This page consolidates identity data verified against PubChem this reference cycle alongside a survey of the peer-reviewed preclinical literature. One important caveat governs the mechanism discussion below: the foundational paper that first established HGF/c-Met dependence for this peptide class was retracted in 2025, so the mechanistic framing here rests only on the remaining non-retracted reports. This material is provided strictly for Research Use Only.
Mechanism Summary
Mechanisms reported in the in-vitro and preclinical research literature include:
- Reported potentiation of the HGF / c-Met receptor tyrosine kinase system in preclinical models
- Augments c-Met phosphorylation at subthreshold HGF levels, engaging downstream PI3K/AKT signaling
- Associated in rodent models with hippocampal spinogenesis and synaptogenesis
- Designed from an Nle-Tyr-Ile AngIV core with N-hexanoyl and C-terminal 6-aminohexanoic amide modifications to raise lipophilicity and reported BBB permeability
- Foundational HGF/c-Met mechanism paper (PMID 25187433) was retracted in 2025; framing rests on remaining non-retracted reports
Reference Data
| Compound name | Dihexa |
|---|---|
| Synonyms | PNB-0408; ATH-1001; Hexanoyl-Tyr-Ile-Ahx-NH2; N-hexanoic-Tyr-Ile-(6) aminohexanoic amide; PubChem CID 129010512; UNII 9WYX65A5C2 |
| CAS | 1401708-83-5 |
| Molecular formula (reported) | C27H44N4O5 |
| Molecular weight | approximately 504.7 g/mol (PubChem CID 129010512; supplier COAs report 504.66 to 504.67, confirm exact value against batch COA) |
| Compound class | Synthetic angiotensin IV (AngIV)-derived oligopeptide analog / small-molecule HGF-c-Met potentiator (N- and C-terminal modified Nle-Tyr-Ile tripeptide core) |
| Physical form | Solid / powder (supplier-listed). Confirm exact form and color against batch COA |
| Purity | Confirm HPLC purity against batch COA |
Identity values are compiled from public chemistry databases and vendor documentation. Confirm the exact salt form, molecular weight, and purity for a given batch against its Certificate of Analysis (COA).
Research Applications
In laboratory research, Dihexa is studied in contexts such as:
- Preclinical rodent cognition and anti-dementia model research (Morris water maze, scopolamine and aged-rat deficits)
- APP/PS1 Alzheimer-model mouse studies of synaptic protein expression, neuroinflammation, and PI3K/AKT signaling
- HGF-mimetic hair-cell protection assays against aminoglycoside ototoxicity in zebrafish lateral line
- HGF-agonist reagent in human pluripotent stem-cell to hepatocyte-like cell differentiation protocols
- Adjunct peripheral-nerve regeneration research in a rat sciatic-nerve repair model
- Huntington's-disease rat 3-NP model research (reported negative result)
- Angiotensin IV / brain renin-angiotensin-system cognition literature reviews
Storage Information
- Store solid powder cold (supplier-listed roughly -20C for around 12 months or 4C for around 6 months); confirm against batch COA
- Store reconstituted stock cold (supplier-listed roughly -20C to -80C for around 6 months)
- Prepare a concentrated DMSO or co-solvent stock, then dilute into aqueous working buffer immediately before use to limit precipitation
- Avoid repeated freeze-thaw of stocks
- See the Lyophilized Storage Guide and Reconstitution Calculator for general cold-chain and reconstitution practice
A Note on Fosgonimeton (ATH-1017)
Dihexa (PNB-0408 / ATH-1001) itself has not entered human clinical trials. The only human data in this space belong to a distinct prodrug, fosgonimeton (ATH-1017), developed by Athira Pharma, which converts in plasma to a related active moiety.
Fosgonimeton clinical results, including the LIFT-AD program (ClinicalTrials.gov NCT04488419), should not be attributed to Dihexa as if they were the same molecule. Fosgonimeton was reported to miss its primary and secondary endpoints in LIFT-AD (announced 2024).
This distinction matters for accurate research framing: no human efficacy or safety data exist for Dihexa itself.
Dihexa is supplied strictly for laboratory and in-vitro research use. It is not for human consumption, veterinary use, or any diagnostic or therapeutic application. Nothing on this page is medical, dosing, or therapeutic advice.