What is Dihexa?
Dihexa (PNB-0408, N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide) is a small angiotensin IV analog studied as a hepatocyte growth factor (HGF) potentiator acting at the c-Met receptor. It sits in the cognitive shelf alongside Semax and Selank, but chemically it has almost nothing in common with them: it is a lipophilic, capped dipeptide-like molecule, not a water-friendly short peptide.
The published work is rodent and cell-culture only. There is no human trial, no human pharmacokinetic dataset, and no clinical programme. The literature also carries a serious integrity caveat, covered under Research Considerations below.
Reconstitution
Dihexa is not water soluble. This is the single most important handling fact about the compound, and it is why the usual BAC-water routine does not apply here. Bacteriostatic water alone leaves the powder cloudy, clumped, or floating undissolved.
The working practice across RUO suppliers and the cell-culture literature is a two-stage co-solvent: dissolve the powder in DMSO first, then dilute the clear DMSO stock with bacteriostatic water to reach the concentration you want.
For a 5mg vial:
- Add 0.5mL DMSO to the vial. This gives a 10mg/mL DMSO stock, the concentration most reference protocols use.
- Once fully clear, add 1.5mL bacteriostatic water slowly.
- Final volume 2mL, final concentration 2.50mg/mL, roughly 25% DMSO by volume.
Add the water slowly and swirl as you go. Dumping water into a concentrated DMSO stock in one shot is the classic way to crash the compound back out of solution. If the mixture turns cloudy, you have diluted too fast or gone too far — see why peptides gel or refuse to dissolve.
Quick Reference
| Parameter | Value |
|---|---|
| Peptide Amount | 5mg |
| Reconstitution Solvent | DMSO, then BAC water (co-solvent) |
| Recommended Volume | 0.5mL DMSO + 1.5mL BAC water (2mL total) |
| Resulting Concentration | 2.50mg/mL |
| Typical Research Dose | varies (preclinical only) |
| Frequency | not established |
Reconstitution Guide
Materials Needed
- Dihexa 5mg lyophilized vial
- DMSO (high purity, anhydrous, sealed — DMSO pulls water out of the air)
- Bacteriostatic water (BAC water)
- Insulin syringes (U-100, 29-31 gauge)
- Alcohol swabs
- Sharps container
Step-by-Step Instructions
- Prepare workspace — Clean environment, gather materials, thorough handwashing. DMSO carries whatever it touches through skin, so work clean and wear gloves.
- Clean vial stoppers — Wipe the Dihexa vial and both solvent containers with alcohol swabs. Allow complete drying.
- Draw DMSO — Draw 0.5mL DMSO with a sterile syringe. Use a dedicated syringe; DMSO can attack some plastics on long contact, so do not park it in a barrel.
- Add to peptide — Inject slowly down the inside wall of the vial, not directly onto the powder.
- Dissolve fully — Swirl gently until the solution is completely clear. Do not move on while anything is still floating. Gentle warming in the hand helps; no shaking.
- Dilute with BAC water — Add 1.5mL bacteriostatic water in stages, swirling between additions.
- Verify — Solution should be clear. Cloudiness means the compound has partly precipitated.
- Label and store — Note the reconstitution date, the solvent ratio, and the final concentration. Refrigerate.
Dosage Protocol
Concentration Calculations
With 5mg peptide in 2mL total volume (0.5mL DMSO + 1.5mL BAC water):
- Concentration: 5mg / 2mL = 2.50mg/mL (2500mcg/mL)
- Per unit (U-100 syringe): 2.50 x 1000 / 100 = 25mcg per unit
The co-solvent does not change the maths — total volume is total volume. What it changes is the handling, so always record the DMSO fraction next to the concentration. Run your own vial and volume combination through the peptide reconstitution calculator to rebuild this table for your setup.
Common Dose Calculations
| Desired Dose | Draw Volume | Syringe Units |
|---|---|---|
| 250mcg | 0.10mL | 10 units |
| 500mcg | 0.20mL | 20 units |
| 1mg | 0.40mL | 40 units |
| 2mg | 0.80mL | 80 units |
Research Considerations
Mechanism
Dihexa was designed as a metabolically stabilised derivative of angiotensin IV, capped at both termini so that peptidases cannot chew it up. It binds HGF with high affinity and is described as potentiating HGF signalling at the c-Met receptor, driving dendritic spine formation and synaptogenesis in hippocampal culture. Rodent work reported reversal of scopolamine-induced spatial memory deficits and improved performance in aged rats.
Two caveats belong on the same page as those claims. First, the key mechanism paper — the 2014 JPET report tying the procognitive and synaptogenic effects to HGF/c-Met activation — was retracted in April 2025 after a university investigation found falsified figure data, and the 2013 characterisation paper carries a 2021 Notice of Concern from the same journal. Second, c-Met is a growth-signalling receptor with a well-known role in tumour biology, which is a large part of why the compound never entered human testing.
That does not mean the compound is uninteresting. It means the evidence base is thinner and shakier than the marketing around it suggests, and anyone reading vendor copy should know which papers are still standing.
Sourcing for Research
Source from verified suppliers that provide third-party testing and certificates of analysis (COA) for each batch. For Dihexa specifically, check whether the listing acknowledges the solubility issue at all — a vendor telling you to reconstitute with plain BAC water has not handled the compound. Some suppliers ship a DMSO ampoule with the vial. Compare purity documentation, shipping conditions, and batch traceability before purchasing research materials.
Storage Requirements
Lyophilized (Powder)
- Temperature: -20°C or colder
- Duration: 2+ years
- Conditions: Dry, dark, tightly sealed and protected from moisture
Reconstituted
- Temperature: 2-8°C (refrigerated)
- Duration: 2-4 weeks
- Conditions: Protected from light, never freeze
One quirk worth knowing: neat DMSO solidifies around 18.5°C, so an undiluted DMSO stock will freeze solid in a fridge. Once diluted to roughly 25% DMSO in water the mixture stays liquid at refrigerator temperature. If you are holding a pure DMSO stock instead, keep it frozen in single-use aliquots and avoid repeated freeze-thaw.
Safety Considerations
- Dihexa is a research compound
- Not approved for any indication in any jurisdiction
- Research use only — not for human consumption
- DMSO is a potent solvent carrier — handle with gloves, avoid skin contact
- Use sterile technique; never reuse needles or syringes
Scientific References
- McCoy AT, et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013;344(1):141-154. (Notice of Concern, J Pharmacol Exp Ther. 2021;378(3):313.)
- Benoist CC, et al. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the HGF/c-Met system. J Pharmacol Exp Ther. 2014;351(2):390-402. Retracted April 2025.
- Cognitive Vitality / Alzheimer’s Drug Discovery Foundation review of Dihexa: no human data, preclinical stage only.
Last updated: 2026-07-21.
Disclaimer: This information is for educational and research purposes only. Dihexa is a research compound and is not approved for any use. Research-grade peptides are not intended for human consumption. Always follow applicable laws and institutional guidelines.