Dihexa (PNB-0408) is a synthetic octapeptide engineered at Washington State University as an angiotensin iv analogue designed to potentiate hepatocyte growth factor signaling through the c-Met receptor. Researchers have studied this compound for its potential role in promoting synaptic growth, supporting memory and recall, and modulating neural pathways associated with age related cognitive decline in rodent models. Its ability to cross the blood-brain barrier and remain active when administered orally has drawn considerable interest from the science community focused on neuroplasticity and brain repair.
Dihexa’s market is composed primarily of research use only vendors, and the compound is intended solely for laboratory research – not to treat, cure, diagnose, or prevent any human disease. No statements on this page should be interpreted as medical advice; individuals seeking treatment should consult a prescribed healthcare provider. Dihexa can be found in various forms including lyophilized powder and oral capsules, with Dihexa 10 mg capsules priced at $649.93 and also available in 5 mg capsules through select suppliers.
General Information About Dihexa
The peptide’s full designation is N-hexanoic-Tyr-Ile-His-Pro-Phe-His-Leu – an 8-amino-acid sequence derived from angiotensin IV with N-hexanoylation at the terminus to increase lipophilicity. These chemical modifications protect the molecule from rapid proteolytic degradation, which is what separates it from native angiotensin IV fragments: those are cleared from serum within minutes, while the modified molecule survives long enough to be dosed on a practical schedule in rodent work. Published magnitudes for that half-life come from a single group and are not quoted here (see the note below).
Dihexa acts as a hepatocyte growth factor/c-Met signaling activator: rather than directly stimulating c-Met on its own, the compound binds HGF and amplifies its engagement with c-Met at subthreshold concentrations. This allosteric mechanism triggers downstream effects in brain cells – increased spinogenesis, dendritic branching, and formation of new synaptic connections – that support learning and cognitive function in preclinical models. Earlier hypotheses centered on IRAP/AT4 receptor action, but subsequent work indicates HGF/c-Met pathways are more central to the observed results.
Dihexa Use in the Research Setting
Dihexa is supplied as a lyophilized hydrophobic powder or in capsule form, intended for research and laboratory use only; its safety and efficacy have been evaluated exclusively in rodent and in vitro studies.
Tendon and Ligament Healing
No published peer-reviewed studies directly assess Dihexa in animal models of tendon or ligament healing. Searches across PubMed and PMC yield no data on extracellular matrix modulation, collagen fiber alignment, or tensile-strength outcomes specific to this compound. Because HGF itself plays a role in tissue repair and fibroblast migration, researchers have expressed interest in whether Dihexa could promote connective-tissue resilience – but that hypothesis remains untested and speculative. Future investigations may address this knowledge gap.
Cognitive and Synaptic Plasticity
Preclinical findings position Dihexa as a potent modulator of synaptic growth and cognitive recall. Work from the Washington State group reported that dissociated hippocampal neurons exposed to picomolar Dihexa formed additional functional synapses, measured as a rise in miniature excitatory postsynaptic current frequency. Important to Know: the central rodent dataset for this compound, McCoy et al. (2013) in JPET, carries a 2021 Notice of Concern from the journal. Specific pharmacokinetic and dose magnitudes from that paper are therefore not quoted on this page; the mechanism described here rests on independent work.
Dihexa promotes neuron growth and new synapse formation through c-Met phosphorylation, which enhances downstream neurotrophic content including BDNF-related signaling. These mechanisms may reduce the risk of age related cognitive decline in preclinical contexts. Dihexa enhances neural signaling and cognitive recall, while also supporting memory, focus, and long-term brain health in animal paradigms. Clients report improved clarity and focus within 2–4 weeks, though such anecdotal observations have not been verified in controlled human trials. The compound’s potential benefits for mental sharpness and attention remain limited to preclinical evidence.
Pharmacokinetics and Stability
Dihexa’s hydrophobic character (high logP) results in extensive tissue distribution – volume of distribution reaches approximately 54.4 L/kg in rats. Researchers should store the lyophilized powder refrigerated, shielded from light; reconstituted solutions degrade quickly and require cold storage. Dissolution typically requires DMSO at less than 1% final concentration for injectable preparations, while aqueous suspensions have been used for oral gavage.
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Model / Route
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Dose Range
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Observed Outcome
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IV (rats)
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rodent PK dosing
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Pharmacokinetic characterization; long terminal half-life
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IP (rats)
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rodent IP range
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Reversal of scopolamine-induced cognitive deficits
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Oral gavage (rats)
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rodent oral and intraperitoneal ranges
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Reported active by the oral route
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Citation capsule: Benoist and colleagues showed in 2014 in JPET that the procognitive and synaptogenic effects of angiotensin IV-derived peptides depend on activation of the hepatocyte growth factor/c-Met system: blocking that system removes the effect, which is what identifies HGF/c-Met rather than IRAP inhibition as the operative pathway.
Dihexa Safe Use Considerations
All safety data for Dihexa is limited to preclinical studies. There are no published Phase 1 or Phase 2 human clinical trials, and Dihexa has no established human dosing regimen or pharmacokinetic profiles in people. Short-term rodent experiments at typical cognition-testing doses did not produce gross organ toxicity, yet long-term carcinogenicity bioassays have never been conducted. The c-Met pathway is implicated in cellular proliferation and tumor growth, making chronic exposure a theoretical concern. Gray-market batches of Dihexa can carry endotoxin contamination, which is why the analytical history of a batch matters before it enters an experiment. Analytical documentation is only meaningful when it names the testing laboratory and the method used – liquid chromatography and mass spectrometry are the usual pair for peptides.
FDA Approved Status
Dihexa is not fda approved for any human use and is classified as investigational by the FDA. Compounded medications like Dihexa are not FDA-evaluated for safety or efficacy, and there is no FDA-approved supply chain for Dihexa for personal use. The compound was removed from the FDA’s Category 2 restricted compounding list, but this does not constitute approval. Dihexa is compounded through licensed U.S. pharmacies in accordance with applicable regulations; most online suppliers sell Dihexa labeled for research use only. No product on this site is intended to diagnose, treat, cure, or prevent any disease in humans.
Other Therapies and Combinations
Compatibility with other therapies and growth-factor modulators has not been rigorously studied. When combined with additional HGF activators or neurotrophic peptides, additive effects are theoretically possible – but so is amplified oncogenic risk, given c-Met’s well-documented role in tumor biology.
<em>Important to Know:</em>
“No formal carcinogenicity studies (2-year rodent bioassays) or chronic toxicology series exist; oncogenic risk remains theoretical but substantial given c-Met’s well-known role in tumor biology.”
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Feature
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Dihexa
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Nle¹-AngIV
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Origin
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Modified AngIV with N-hexanoyl cap; 8 residues
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AngIV fragment with norleucine substitution; less modified
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Half-life (rat, IV)
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Days rather than minutes
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Native AngIV: cleared within minutes in serum
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Oral activity
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Reported active via oral gavage
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Poor oral bioavailability; rapid degradation
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Mechanism
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Allosteric HGF/c-Met potentiation at sub-threshold HGF
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Procognitive via IRAP; requires higher doses
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Supplied for research use only, to licensed professionals.
All Dihexa products on this page are supplied for research and laboratory use only. These statements have not been reviewed by the FDA; nothing on this site is intended to diagnose, treat, cure, or prevent any disease.
Related research peptides available at FillerSupplies.com: Semax, Selank, PE-22-28.
FAQ
Is Dihexa Safe for Research Use?
Safety data for Dihexa is limited to preclinical and in vitro studies; no human clinical trials have been completed. Short-term rodent studies at standard cognition-testing doses did not reveal acute organ toxicity. However, the c-Met pathway's involvement in cellular proliferation means long-term oncogenic risk has not been ruled out, so researchers should handle the compound with appropriate caution.
How Does Dihexa Work - HGF or IRAP?
Dihexa binds hepatocyte growth factor and potentiates its interaction with the c-Met receptor at subthreshold concentrations, triggering downstream synaptogenesis and spinogenesis in neurons. While earlier angiotensin IV analogues were thought to act primarily through IRAP inhibition, evidence from Benoist et al. (2014) points to HGF/c-Met engagement as the more relevant pathway for the cognitive effects observed in rodent models.
How Does Dihexa Compare to Nle¹-AngIV?
Dihexa's chemical modifications leave it far more resistant to proteolysis than native angiotensin IV fragments, which are cleared from serum within minutes, and it has been reported active by the oral route in rodent cognition work, whereas Nle¹-AngIV shows poor oral bioavailability and typically requires central administration. These pharmacokinetic advantages make Dihexa a more practical tool for longer-duration preclinical protocols.
What Dose Ranges Have Been Studied in Animal Models?
Published rodent protocols used both intraperitoneal and oral routes in scopolamine-deficit models. Specific dose figures are not reproduced here because the rodent dataset behind them carries a journal Notice of Concern; researchers should take them from the primary literature and judge it for themselves. No established human dosing regimen exists.
How Should Dihexa Be Stored and Reconstituted?
Store lyophilized Dihexa powder refrigerated and protected from light. Reconstitution typically requires DMSO at less than 1% final concentration for injectable protocols. Reconstituted solutions are unstable and should be used promptly; discard any preparation showing turbidity.
Is Dihexa a Prohibited Substance Under WADA?
WADA bans certain exogenous growth-factor modulators, and Dihexa's function as an HGF/c-Met potentiator could place it under prohibited categories. Researchers involved in any sport-adjacent or anti-doping-regulated work should verify the compound's current classification before use.
Researchers looking to buy dihexa online can find authentic, quality-controlled products at FillerSupplies.com. The site offers temperature-controlled shipping, express worldwide dispatch, and expert support for licensed professionals seeking to dihexa peptide buy usa for laboratory investigations.
