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Catalog/Dihexa

Dihexa

Also known as PNB-0408 · N-hexanoic-Tyr-Ile-(6) aminohexanoic amide

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

Research refreshed

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.

Background

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.

Key research findings

  • 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.

How Dihexa is made

Behind every vial of Dihexa is the same exacting pipeline every research peptide runs — but the chemistry plays out differently for this molecule. Here is how Dihexa, specifically, is brought into being.

  1. On paper first

    On paper, Dihexa is C27H44N4O5 — about 504.7 daltons of precisely arranged atoms. Before a single bond is made, the target sequence, salt form, and purity threshold are written down as the contract the finished material must meet.

  2. Built residue by residue

    Dihexa is assembled by solid-phase peptide synthesis — the chain grows one protected residue at a time on resin, and what you fail to build cleanly here you pay to remove later.

  3. Purity is won here

    The crude mixture — Dihexa plus its deletions and side products — is then separated on preparative HPLC, and where the cut is taken decides the difference between a genuinely pure peptide and a barely-passable one.

  4. Proven, then protected

    A real batch of Dihexa proves itself: identity confirmed by mass spectrometry against its ~504.7 Da, purity read directly off an analytical HPLC trace, water and counterion content measured. That batch-specific certificate of analysis is the only honest way to know what is actually in a vial of Dihexa — and a short, cold, accountable chain of custody is how that purity survives the trip to your bench.

Walk the full synthesis pipeline

Handling, storage & why purity is hard

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.

Moderate synthesisUnnatural residue

Don't judge a vial by its cake. A fluffy, good-looking lyophilized powder reflects bulking agents and freeze-drying parameters — not purity. Insist on a batch-specific certificate of analysis.

How peptides are made — the full pipeline

Research areas

  • Cognition
  • Synaptogenesis
  • Neurodegeneration

Research-area guides

Frequently asked questions

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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