# Dihexa

> An orally active angiotensin IV–derived peptidomimetic reported as an extraordinarily potent synaptogenic (synapse-forming) compound.

- Also known as: PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide
- Class: Cognitive
- FDA approved: No
- Canonical page: https://americanpeptide.com/catalog/dihexa

## Overview

Dihexa is a small peptidomimetic derived from angiotensin IV, developed to promote the formation of new synapses. It works through the hepatocyte growth factor (HGF) / c-Met system rather than a classic neurotransmitter pathway, and it was reported in preclinical work to be orders of magnitude more potent than BDNF at driving synaptogenesis — which is why it draws intense interest as a cognitive research compound despite very limited human data.

Dihexa came out of work by Joseph Harding and colleagues at Washington State University on angiotensin IV, a fragment of the blood-pressure hormone angiotensin that unexpectedly turned out to support learning and memory. The team engineered a stabilized, orally active, blood–brain-barrier-penetrant derivative — Dihexa — designed to keep the pro-cognitive activity while surviving in the body long enough to matter.

Its headline claim is potency: in preclinical assays Dihexa was reported to promote new synapse formation at concentrations far below those needed by brain-derived neurotrophic factor (BDNF), acting by enhancing signaling of hepatocyte growth factor (HGF) through its receptor c-Met. That mechanism and potency make it a compelling research tool for neurodegeneration, but the same properties — a small molecule that powerfully drives cell signaling — mean its safety is essentially uncharacterized in humans. It is a research compound and is not FDA-approved.

## Mechanism

Proposed potentiation of hepatocyte growth factor (HGF) signaling at its receptor c-Met, promoting synaptogenesis; derived from the angiotensin IV / AT4 system.

## Chemistry

| Property | Value |
| --- | --- |
| Molecular formula | C27H44N4O5 |
| Molecular weight | 504.7 Da |
| CAS number | 1401708-83-5 |
| PubChem CID | [129010512](https://pubchem.ncbi.nlm.nih.gov/compound/129010512) |

## Research areas

Studied in: Cognition, Synaptogenesis, Neurodegeneration.

Guides on this site:

- [Cognition & Neuroprotection](https://americanpeptide.com/research-areas/cognition-neuroprotection): Nootropic and neurotrophic peptides studied for cognition and recovery.

## Key research

- Synaptogenesis — reported in preclinical work to promote new synapse formation with very high potency (orders of magnitude beyond BDNF in the original assays).
- HGF / c-Met mechanism — proposed to work by potentiating hepatocyte growth factor signaling at the c-Met receptor.
- Angiotensin IV origin — engineered from the pro-cognitive AT4-system peptide angiotensin IV for oral activity and brain penetration.
- Neurodegeneration research — studied as a candidate for cognitive-decline models; human data are very limited.
- Not FDA-approved — an early-stage research compound with an uncharacterized human safety profile.

## Storage, handling & synthesis

**Synthesis.** Dihexa is a peptidomimetic — a modified dipeptide core (Tyr-Ile) capped with an N-terminal hexanoyl group and a C-terminal 6-aminohexanoic amide — rather than a standard peptide. It is assembled by short solid-phase / solution steps, but the non-amino-acid caps mean its identity and related-substance control resemble small-molecule QC as much as peptide purity.

## FAQs

### What is Dihexa?

Dihexa is an orally active peptidomimetic derived from angiotensin IV, studied as a highly potent promoter of new synapse formation via the HGF / c-Met pathway.

### Why is it considered so potent?

In the original preclinical assays it promoted synaptogenesis at concentrations orders of magnitude lower than BDNF, a benchmark neurotrophic factor.

### How does it work?

It is proposed to enhance hepatocyte growth factor (HGF) signaling through the c-Met receptor, rather than acting on a classic neurotransmitter system.

### Is Dihexa safe or approved?

No — it is an early-stage research compound, not FDA-approved, and its safety in humans is essentially uncharacterized. This page is a research and educational reference.

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Source: AmericanPeptide.com — https://americanpeptide.com/catalog/dihexa
Data license: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Attribution: AmericanPeptide.com.
Research reference only — computational and educational content, not medical advice.