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Dihexa (PNB-0408)

Also known as PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, Dihexa acetate, angiotensin IV analog

Preclinical only

Investigational angiotensin IV analog; hepatocyte growth factor (HGF)/MET positive modulator (preclinical)

Not FDA-approved. Not on FDA's 503A category lists (May 14, 2026). Source, May 14, 2026

Identity. Dihexa is the research code PNB-0408, the synthetic angiotensin IV (AngIV) analog N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (PMID 38489193). FDA's compounding page names it as dihexa acetate. No ambiguity found about the molecule. It is an investigational research compound, not an approved drug; the product name does not denote any approved product.

At a glance

These dosages are a helpful guide, not a prescription. Every clinician is expected to do their own due diligence before prescribing.

No established human dose

The evidence is preclinical only. PubMed lists rodent studies of cognition, nerve injury and a Huntington disease model, plus zebrafish work. No human trial, human pharmacokinetic data or human dosing was found. Two foundational Washington State University papers carry retraction notices (2025) and an expression of concern (2021). One rat Huntington model study found no benefit. FDA states it has identified no human exposure data for dihexa acetate. A 2018 systematic review of experimental non-human studies (PMID 29733881) is the best single summary of the animal evidence. Papers that use dihexa as a reagent to turn human stem cells into liver cells are in vitro work and are not clinical evidence.

No human dosing exists; evidence is preclinical only, and a key 2014 paper was retracted in 2025.
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Dosing detail

Clinical practice

Clinical practice

No citable clinician dosing found. No peer-reviewed review, compounding protocol, professional education material or textbook gives a human dose. The only dosing pages found were gray-market or aggregator sites. The best of these (Peptide Protocol Wiki, updated 02/12/2026) states 'Human-equivalent doses cannot be reliably calculated from these data' and gives no human dose, so none is listed. A 2026 orthopaedic peptide review (PMID 41490200) names dihexa but states 'there is a current lack of clinical trials'.

Safety

Serious warnings

  • FDA: 'FDA has not identified any human exposure data on drug products containing dihexa acetate administered via any route of administration.' Human safety is not characterized.1
  • Theoretical and mechanism-based; not observed in humans. Dihexa is proposed to potentiate HGF/c-Met signaling. The dihexa developers' own review states 'Activation of the c-Met receptor stimulates mitogenesis, motogenesis, morphogenesis...' (PMID 25649658), and a 2026 oncology review describes the HGF/C-MET pathway as 'involved in various processes such as tumor cell growth, invasion, migration, angiogenesis' (PMID 42575887). No human study has examined whether dihexa carries this risk, and the paper describing the mechanism has been retracted. A personal history of malignancy is a reason for extra caution. This is a prescriber consideration, not a labeled contraindication.2
  • FDA also states it lacks information about safety issues for dihexa acetate, including whether it could harm humans. Absence of data is not absence of harm.1

Contraindications

  • Not studied in humans. No labeled contraindications exist. That does not mean none apply.1

Adverse effects

  • Not studied in humans. No human adverse-effect data exist.1

Monitoring

  • No validated monitoring exists because there are no human data.1

Interactions

  • Not studied in humans.1

Evidence

The evidence is preclinical only. PubMed lists rodent studies of cognition, nerve injury and a Huntington disease model, plus zebrafish work. No human trial, human pharmacokinetic data or human dosing was found. Two foundational Washington State University papers carry retraction notices (2025) and an expression of concern (2021). One rat Huntington model study found no benefit. FDA states it has identified no human exposure data for dihexa acetate. A 2018 systematic review of experimental non-human studies (PMID 29733881) is the best single summary of the animal evidence. Papers that use dihexa as a reagent to turn human stem cells into liver cells are in vitro work and are not clinical evidence.

Mechanism

In rodent and cell studies, dihexa is described as an AngIV analog that crosses the blood-brain barrier and enhances HGF dimerization. This increases MET receptor signaling and activates PI3K/AKT downstream. The original mechanism paper (PMID 25187433) has since been retracted, so the HGF/MET mechanism now rests on later, smaller studies.23456

Availability

Amounts offered

  • 10 mg

Custom strengths on request.

References

According to PubMed

  1. 1FDA: Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026)U.S. Food and Drug Administration, 2026
  2. 2The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's DiseaseJ Alzheimers Dis, 2015
  3. 3Hepatocyte Growth Factor/MET Activator Rescues Working Memory Deficits after Repeated Mild Traumatic Brain InjuryNeurotrauma Rep, 2025
  4. 4AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling PathwayBrain Sci, 2021
  5. 5The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System (RETRACTED 2025)J Pharmacol Exp Ther, 2014
  6. 6Retraction 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, 2025
  7. 7Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in RatsJ Huntingtons Dis, 2024
  8. 8Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model: Experimental animal studiesAnn Med Surg (Lond), 2021
  9. 9Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future DirectionsJ Am Acad Orthop Surg Glob Res Rev, 2026
  10. 10Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposureFront Cell Neurosci, 2015
  11. 11Notice of Concern: McCoy AT et al. (2013) Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia Agents (original article PMID 23055539, DOI 10.1124/jpet.112.199497)J Pharmacol Exp Ther, 2021
  12. 12FDA: Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act (content current as of 05/14/2026)U.S. Food and Drug Administration, 2026
  13. 13Dihexa dosing (Peptide Protocol Wiki, updated 02/12/2026); aggregator, not used for any dosepeptideprotocolwiki.com, 2026
  14. 14C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapySignal Transduct Target Ther, 2026
  15. 15Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studiesNeurosci Biobehav Rev, 2018

Last reviewed 2026-10-14. 6 figures checked against their sources. How this works