Compounds / Dihexa
Dihexa
Also known as: PNB-0408; N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide; Hexanoyl-Tyr-Ile-Ahx-NH2; PubChem CID 11527385
Primary research focus: Cognitive and neuroplasticity research (angiotensin IV-derived HGF/c-Met modulator)
Last updated July 2026 · Reviewed against FDA labeling and published research.
What is Dihexa?
Dihexa is a small synthetic peptidomimetic derived from angiotensin IV, engineered at Washington State University for metabolic stability and blood-brain-barrier penetration. It has been studied preclinically as a potentiator of hepatocyte growth factor (HGF) signaling at the c-Met receptor, a pathway linked to synaptogenesis and cognition. It is a research compound with no FDA approval and no human data; importantly, several foundational mechanism papers were retracted for data integrity problems.
Dihexa was proposed to bind HGF and potentiate its activity at the c-Met receptor, driving dendritic spine formation and synaptogenesis in preclinical models. This HGF/c-Met framing is now uncertain: the key mechanistic papers (Kawas et al. 2012 and Benoist et al. 2014) were retracted in April 2025 for falsified or fabricated data, and the foundational behavioral paper (McCoy et al. 2013) carries a Notice of Concern. At least one independent study (Sun et al. 2021) corroborated pro-cognitive effects but attributed them to a different pathway (PI3K/AKT). The true molecular mechanism should be considered unresolved.
How it’s supplied
Not an FDA-approved or commercially manufactured medicine. It is distributed exclusively through gray-market research-chemical vendors as a research-grade compound (powder or solution). Such products are not FDA-reviewed for identity, potency, or sterility, and independent surveillance has found frequent quality failures in this category.
Dosage Chart
Units shown are for a U-100 insulin syringe (100 units = 1 mL), calculated from the vial size and BAC water you select. Always confirm against your prescription and your syringe markings.
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Weeks 1-4 | 0.5 mg/kg | 1x Daily | — |
| Weeks 5-8 | 1.0 mg/kg | 1x Daily | — |
- Rotate injection sites to reduce irritation and lipohypertrophy
- Not for use during pregnancy or breastfeeding
- Do not exceed the recommended dose to try to speed results
Potential Benefits and Side Effects
Effects reported in published research. Not a promise of results, and not medical advice.
- Reported in preclinical (rodent and cell) research only; human efficacy is not established and key mechanistic data were retracted.
- Improved spatial learning and memory in aged and scopolamine-treated rats.
- Reported promotion of dendritic spine formation and synaptogenesis in preclinical models.
- High reported neurotrophic potency at very low concentrations in laboratory assays.
- No human adverse-effect data are available.
- Short-duration animal studies did not report overt toxicity, but long-term safety in any species is not established.
- A theoretical oncogenic concern exists given the c-Met/HGF pathway's role in cell proliferation.
Warnings and contraindications
Important safety information. This is not exhaustive — read the full prescribing information and consult your prescriber or pharmacist.
- No FDA-approved labeling exists; the following reflect the compound's status and the limits of its evidence, not established label warnings.
- There are no human clinical trials or published human safety data for dihexa.
- Key mechanistic papers were retracted in April 2025 for data fabrication, and the foundational behavioral paper carries a Notice of Concern; the evidence base is significantly weakened.
- The HGF/c-Met pathway is implicated in cancer biology, raising a theoretical oncogenic concern with chronic activation.
- Dihexa has an unusually long reported serum half-life, so any adverse effects could persist for weeks after stopping.
- Gray-market material varies widely in identity and purity.
- Not established; no FDA-approved labeling. Precautionary considerations include active or suspected malignancy (theoretical concern given c-Met/HGF biology) and known hypersensitivity.
Reconstitution Steps
How to prepare the lyophilized vial. Confirm specifics with your pharmacist or prescriber.
- Confirm the amount of peptide in the vial and the volume of diluent you intend to use before starting.
- Wash your hands and gather supplies: the lyophilized vial, the diluent (typically bacteriostatic water), an alcohol swab, and a sterile syringe.
- Let the vial and diluent reach room temperature if they were refrigerated or frozen.
- Wipe the rubber stopper of both the peptide vial and the diluent vial with a fresh alcohol swab and let them air dry.
- Draw the intended diluent volume into the syringe.
- Insert the needle into the vial and slowly release the diluent down the inside wall rather than directly onto the powder, to avoid foaming.
- Do not shake. Gently swirl or roll the vial until fully dissolved.
- Inspect the solution: it should be clear and colorless with no visible particles. Do not use if cloudy or containing particles.
- Note the resulting concentration (amount divided by diluent volume) so it matches the reconstitution calculator on this page.
- Label the vial with the reconstitution date and store as directed under reconstituted storage.
US regulatory status
Classifications are public record but can change. For reference only, not legal advice.
Development: Dihexa (PNB-0408) emerged from a Washington State University program (John Wright and Joseph Harding) developing metabolically stable, CNS-penetrant analogs of angiotensin IV. Preclinical work reported cognitive restoration in aged and scopolamine-treated rodents. The program's mechanistic foundation was later compromised: Kawas et al. (2012) and Benoist et al. (2014) in the Journal of Pharmacology and Experimental Therapeutics were formally retracted in April 2025 after a university investigation found falsified or fabricated data, and McCoy et al. (2013) carries a Notice of Concern. A separately developed prodrug, fosgonimeton (ATH-1017), reached FDA-regulated clinical trials for Alzheimer disease under a different sponsor; dihexa itself has no IND, no approval, and no human data as of mid-2026.
Notes: Dihexa is not FDA-approved and has no recognized clinical use. It has no IND or NDA and is sold only as a research chemical through gray-market vendors, outside FDA quality oversight. It is not on the FDA 503A bulk drug substances list and is not eligible for 503A or 503B compounding. It is not a controlled substance.
International status
Pharmacokinetics
Storage and handling
Important Notes
Practical considerations for consistency and safety.
- The foundational HGF/c-Met mechanism papers for dihexa were retracted in 2025 for data fabrication; the mechanism and much of the original evidence are in question.
- There are no human trials or human safety data.
- Its prodrug fosgonimeton (ATH-1017) is a separate compound that reached clinical trials; do not conflate the two.
- The reported half-life is very long, so effects and any adverse events could persist for weeks.
- Gray-market material varies widely in identity and purity.
Lifestyle Factors
- Reported to be orally active in preclinical models.
- Human lifestyle interactions are unstudied.
References
Related compounds
Important disclaimer
This page is an educational reference, not medical advice, a diagnosis, or a treatment recommendation, and not a substitute for your prescriber or pharmacist. Approval and regulatory status varies by compound and can change. Always confirm against current prescribing information and consult a qualified healthcare professional before making any decision about a medication.