Research Only Cognitive & Nootropic

Dihexa

also known as: PNB-0408, N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide

A synthetic angiotensin-IV-derived peptide studied for potent synaptogenic activity via HGF/c-Met pathway — but the foundational research has been called into question and no human safety data exists.

An orally available, BBB-penetrant synthetic hexapeptide developed at Washington State University as a stabilized analog of angiotensin IV, promoted for its reported potency in inducing synaptogenesis via the HGF/c-Met receptor pathway in hippocampal models.

Mechanism of action

Reported to augment hepatocyte growth factor (HGF) binding to the c-Met receptor, promoting synaptogenesis and dendritic spine formation in hippocampal neurons. Promoted as orders of magnitude more potent than BDNF in preclinical synaptogenesis assays. Because c-Met activation is oncogenic in many cancers, there is a theoretical concern about tumor promotion with chronic use.

Primary uses

Preclinical cognitive enhancement research
Neurodegenerative disease research (early)

Typical dosing

8–45 mg daily (oral (community))

Community dosing only. No human clinical trial has established safety or efficacy. Theoretical cancer risk from c-Met activation warrants caution.

Regulatory status

Not approved. Preclinical-stage research peptide. Seminal synaptogenesis paper (Benoist 2014) has had methodological critiques and the HGF/c-Met mechanism underpinning Dihexa's reputation has been subject to retractions in the broader field. Commercial development has not advanced.

References

[pubmed] Benoist CC, et al. "Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs." J Pharmacol Exp Ther, 2014;351:390-402.
[pubmed] McCoy AT, et al. "Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents." J Pharmacol Exp Ther, 2013;344:141-154.

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Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.