Dihexa
Also known as: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, Norleual
Grey-Market Compound. This compound is not approved by the FDA or any major regulatory authority. No established regimen exists. Products available outside of regulated channels lack standardized manufacturing, quality control, and potency verification. Consult a qualified clinician. Research-only risks apply.
Overview
Clinical Summary
Dihexa is a hexapeptide analogue of angiotensin IV developed at Washington State University. It was designed to enhance hepatocyte growth factor (HGF) signaling through the c-Met receptor, a pathway implicated in synaptogenesis and neuronal survival. In preclinical rodent models, dihexa demonstrated cognitive enhancement at extremely low doses (subpicomolar potency), making it one of the most potent nootropic compounds ever tested in animal models. However, no human clinical trials have been conducted, and its safety profile in humans is entirely unknown.
Plain Language Summary
Dihexa is a research peptide that was developed to improve brain function by boosting a growth factor pathway involved in forming new brain connections. In animal studies, it improved memory and learning at remarkably low doses. It has never been tested in humans, and its safety in people is completely unknown. It is available only through grey-market sources without any quality assurance.
Mechanism of Action
Dihexa is a modified hexapeptide derived from angiotensin IV that acts as an allosteric potentiator of the HGF/c-Met receptor system. Rather than directly activating c-Met, dihexa enhances the binding of endogenous hepatocyte growth factor to its receptor, promoting receptor dimerization and downstream signaling. This results in activation of PI3K/Akt and Ras/MAPK pathways, which promote dendritic spine formation, synaptogenesis, and neuronal survival. The subpicomolar potency suggests an extremely high-affinity interaction with the HGF/c-Met complex. Dihexa crosses the blood-brain barrier and is active via oral, subcutaneous, and intranasal routes in rodents.
Evidence Summary
All evidence for dihexa is preclinical. McCoy et al. (2013) showed that dihexa reversed scopolamine-induced cognitive deficits in rats and restored dendritic spine density in the hippocampus. Benoist et al. (2014) demonstrated that both oral and subcutaneous dihexa improved cognitive performance in aged rats and an Alzheimer disease model. These studies originate from a single laboratory group at Washington State University. No independent replication has been published. No human pharmacokinetic, pharmacodynamic, or safety studies exist.
Safety Profile
The safety profile of dihexa in humans is entirely unknown. No toxicology, mutagenicity, or carcinogenicity studies have been published. A significant theoretical concern is that potentiation of HGF/c-Met signaling could promote tumor growth, as aberrant c-Met activation is implicated in multiple cancers. The lack of any human data makes risk assessment impossible.
Contraindications
- No established contraindications due to absence of human data
- Theoretical concern in any history of cancer (HGF/c-Met pathway is oncogenic)
- Pregnancy and breastfeeding (no safety data)
Adverse Events
- No human adverse event data available
- Theoretical oncogenic risk from HGF/c-Met pathway potentiation
- Unknown cardiovascular effects (angiotensin system derivative)
Interactions
- No drug interaction data available
- Theoretical interaction with other angiotensin system modulators (ACE inhibitors, ARBs)
- Unknown interactions with oncology therapeutics targeting c-Met
Regulatory Notes
Dihexa has no regulatory approval in any jurisdiction. It has not entered clinical trials. It is available through grey-market peptide suppliers without manufacturing quality controls. The FDA has not issued specific guidance on dihexa, but it would be considered an unapproved new drug.
Monitoring Considerations
No established monitoring guidelines. Given the mechanism of action, clinicians in research settings may consider baseline and periodic cancer screening, liver function tests, and cardiovascular monitoring. However, no validated monitoring protocol exists for this compound.
These are general considerations for clinical awareness and do not constitute prescriptive monitoring recommendations for any individual patient.
Stability and Handling Notes
No pharmaceutical-grade stability data available. Grey-market preparations are typically supplied as lyophilized powder requiring reconstitution with bacteriostatic water. Storage recommendations from vendors (not validated) suggest refrigeration at 2 to 8 degrees C after reconstitution. No USP or pharmacopeial standards exist.
References
- 1preclinical
Angiotensin IV Analog Dihexa Rescues Cognitive Deficits and Dendritic Spine Loss in a Scopolamine Model of Dementia
McCoy AT, Benoist CC, Wright JW, et al. (2013). Molecular Brain
Key findings: Dihexa improved cognitive performance in scopolamine-treated rats and reversed dendritic spine loss in the hippocampus. Demonstrated subpicomolar potency in augmenting HGF/c-Met receptor dimerization.
Limitations: Rodent study only. No human pharmacokinetic or safety data available. Single lab group.
View source - 2preclinical
Dihexa, a Small Molecule with HGF/c-Met Enhancing Activity, Reverses Cognitive Deficits in Rodent Models
Benoist CC, Kawas LH, Zhu M, et al. (2014). Journal of Pharmacology and Experimental Therapeutics
Key findings: Oral and subcutaneous dihexa restored cognitive function in aged rats and in a rat model of Alzheimer disease. Acts through potentiation of HGF/c-Met signaling to promote synaptogenesis.
Limitations: Animal data only. No toxicology studies published. Potential oncogenic risk from HGF/c-Met pathway activation not evaluated.
View source
Last reviewed: 2026-03-24 | Version: 1 | Status: Published
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