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All peptides

Cognitive · Research Phase

Dihexa

No lawful US pathway

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Written by Peptide Association Editorial TeamLast reviewed Editorial policy

01 · Overview

Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide, also called PNB-0408) is a small synthetic angiotensin IV analogue rather than a true hexapeptide (PMID 38489193). Its developers reported that it is metabolically stable, crosses the blood-brain barrier, and augments synaptic connectivity, proposing that it acts through the hepatocyte growth factor (HGF)/c-Met system (PMID 25455861).

However, a key paper reporting HGF/c-Met dependence was retracted in 2025 (PMID 40312093), and an earlier paper from the same group received an expression of concern (PMID 34551989).

02 · Research summary & key findings

An independent study reported that oral dihexa restored spatial learning and reduced neuroinflammation in APP/PS1 Alzheimer model mice (PMID 34827486), while another found it did not protect rats from Huntington disease-like deficits (PMID 38489193). Much of the foundational work comes from the developing laboratory and has been subject to retraction or concern notices. No human clinical trials have been published, and human safety and efficacy data are absent.

03 · Regulatory status

Dihexa is in the research phase with limited clinical data in humans. Current evidence is primarily derived from preclinical (animal or in vitro) studies.

No lawful pathway today

Dihexa is not FDA-approved and does not currently have a lawful prescription or compounding pathway in the United States, so we do not sell it and will not book a consultation for it. That can change: in 2026 FDA began reviewing several peptides for compounding. If you are working on the goal it is studied for, a licensed clinician can tell you what is lawfully available, which may be something else.

Tell me if the status changes

One email, only if this compound's regulatory standing actually moves. Not a newsletter, not a sales sequence.

Looking for a lawful, clinician-prescribed option for cognitive support?

Dihexa is a research compound, is not FDA-approved, and has no lawful US compounding pathway, so we do not offer it and no clinician we work with will prescribe it. Products sold online as “research chemicals” are not made or tested to the standards required of medicines. If you are working on cognitive support, a licensed clinician can tell you at a free consultation whether an FDA-approved or lawfully compounded treatment fits you, or whether nothing does.

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04 · Administration routes

  • Oral
  • Subcutaneous injection

References

  1. [1]The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases Prog Neurobiol, 2015. PMID 25455861
  2. [2]Notice of Concern: McCoy AT, Benoist CC, Wright JW, Kawas LH, Bule-Ghogare JM, Zhu M, Appleyard SM, Wayman GA, and Harding JW (2013) Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia Agents, J Pharmacol Exp Ther, 344: 141-154; DOI: https://doi.org/10.1124/jpet.112.199497 J Pharmacol Exp Ther, 2021. PMID 34551989
  3. [3]AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway Brain Sci, 2021. PMID 34827486
  4. [4]Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats J Huntingtons Dis, 2024. PMID 38489193
  5. [5]Retraction notice to "The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System" [J Pharmacol Exp Ther 351 (2014) 390-402] J Pharmacol Exp Ther, 2025. PMID 40312093

Primary literature

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Disclaimer: This information is provided for educational and research purposes only. It is not intended as medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting any peptide therapy. The Peptide Association does not endorse or recommend any specific treatment protocol. See our editorial policy for how this content is produced and reviewed. Clinicians: join the network.