Dihexa
Also known as: N-Hexanoic-Tyr-Ile-(6)-aminohexanoic amide · PNB-0408
An orally active hexapeptide derivative of angiotensin IV, characterised in academic research as among the most potent known pro-cognitive compounds in animal models.
- Category
- Neurogenesis
- Half-life
- Oral bioavailability with extended pharmacodynamic effects
- Formula
- C₂₆H₄₃N₅O₅
- Weight
- 521.66 g/mol
Section 1
Overview
Dihexa is a small hexapeptide derivative engineered from the C-terminal fragment of angiotensin IV, designed at Washington State University to be orally bioavailable, blood-brain-barrier penetrant, and metabolically stable. The molecule is positioned in academic research as a tool for studying hepatocyte growth factor (HGF) / c-Met signalling in the central nervous system.
The compound's defining property in published research is its capacity to promote new synaptic connections — synaptogenesis — at sub-nanomolar concentrations in hippocampal slice preparations. Researchers have reported potency several orders of magnitude greater than BDNF in head-to-head spinogenesis assays.
Dihexa has been profiled in animal models of cognitive impairment, including scopolamine-induced amnesia and aged-rat learning paradigms, where it has been reported to restore performance to that of young, untreated control animals.
Section 2
Discovery & History
- Developed by Joseph Harding's group at Washington State University in the 2010s as part of a broader programme exploring angiotensin IV's CNS effects.
- First major publications describing potent synaptogenic activity appeared between 2012 and 2015.
- The molecule remains a research compound: no clinical trials are publicly registered, and it is not in any regulatory approval pipeline known to date.
- Has acquired interest in academic and laboratory research circles for its reported oral bioavailability — unusual for a peptide of this size.
Section 3
Mechanism of Action
- 1Activates the hepatocyte growth factor (HGF) / c-Met signalling pathway in central neurons. HGF/c-Met is a well-characterised driver of dendritic spine formation and synaptic remodelling.
- 2Promotes dendritic spine density increases in hippocampal pyramidal neurons in published in vitro work, at picomolar to nanomolar concentrations.
- 3Stabilises HGF dimers, prolonging the active signalling species and producing sustained pro-synaptogenic stimulus.
- 4Downstream effects include activation of the PI3K-Akt and MAPK pathways, both implicated in long-term potentiation and memory consolidation.
- 5Has been reported to facilitate long-term potentiation (LTP) in hippocampal slice electrophysiology — the cellular correlate of learning.
Section 4
Researched Benefits
Findings reported in the published preclinical and clinical literature. Effects in research contexts do not constitute claims of therapeutic benefit in humans.
- 1Restoration of cognitive performance in aged-rat learning paradigms in published work.
- 2Reversal of scopolamine-induced amnesia in rodent models.
- 3Promotion of dendritic spine density in hippocampal neurons.
- 4Reported oral bioavailability — distinctive among small peptides.
- 5Facilitation of long-term potentiation in hippocampal preparations.
- 6Potential research utility in neurodegenerative disease modelling.
Section 5
Theoretical Dosing & Protocols
| Route | Dosage | Frequency | Duration |
|---|---|---|---|
| Oral (research) | Animal study doses scale broadly across the literature; no validated human protocol exists | Once daily in most rodent protocols | Study durations vary; chronic dosing has been examined in animal work only |
Note: Human pharmacokinetic data is not available in published peer-reviewed sources.
Section 6
Administration Routes
- Oral — the molecule's defining feature is its capacity to survive enteric proteolysis and reach the CNS after oral administration in animal research.
- Sublingual and transdermal routes have been explored in laboratory work; results in the literature are limited.
Section 7
Safety Profile
Commonly reported
- · Limited safety data — human pharmacovigilance data is not available
- · Theoretical considerations relate to systemic activation of c-Met signalling
Rare / theoretical
- · c-Met activation is implicated in oncogenic signalling pathways — long-term mitogenic implications have not been characterised in published human research and constitute a meaningful theoretical concern.
- · No long-term toxicology data in any species is publicly available
Contraindications
- · Not authorised for human use in any jurisdiction
- · Theoretical contraindication in any subject with active or historic malignancy, given c-Met pathway involvement
- · No data in pregnancy, lactation, or developmental contexts
Section 8
UK & EU Regulatory Context
United Kingdom
Not a licensed medicine. Research chemical for laboratory and preclinical use only.
European Union
Not approved by the EMA. No clinical authorisation in any EU jurisdiction.
Section 9
Clinical Studies Summary
Dihexa as a synaptogenic agent — hippocampal slice study
Application of Dihexa at sub-nanomolar concentrations produced robust increases in dendritic spine density in hippocampal pyramidal neurons.
Reversal of scopolamine amnesia in rats
Oral Dihexa restored learning performance in a scopolamine-amnesia model to control levels.
HGF/c-Met activation as the molecular basis of Dihexa's effects
Mechanistic dissection demonstrating that Dihexa's pro-cognitive effects are abolished by c-Met receptor antagonism.
Section 10
Frequently Asked Questions
Section 11
Sourcing for Laboratory Research
Sourcing Dihexa for laboratory research
Researchers in the United Kingdom and elsewhere typically obtain Dihexa from specialist research-chemical suppliers. Purity, third-party testing, and supplier transparency are the principal differentiators worth evaluating before placing an order. The two suppliers below are commonly referenced in UK research contexts.
Reminder: research peptides are sold strictly for in vitro and preclinical laboratory purposes. Importation or supply for human consumption is not permitted under UK medicines legislation.