Dihexa (PNB-0408) (PNB-0408)
Angiotensin IV-derived HGF/c-Met modulator studied for cognition in animals; key 2014 JPET paper retracted in 2025; FDA: no human exposure data.
60-Second Scientific Briefing
Dihexa is a small modified peptide derived from angiotensin IV, studied in experimental animals for memory and cognition. Evidence comes only from experimental animals, and the key 2014 paper on its mechanism (J Pharmacol Exp Ther) was retracted in 2025 after an expression of concern in 2021. Not approved by the US FDA or any other regulator; it is a research compound.
What is Dihexa (PNB-0408)?
Pharmacological Classification & Molecular IdentityDihexa is a small modified peptide derived from angiotensin IV, studied in experimental animals for memory and cognition. [1] J Pharmacol Exp Ther, 2014 ↗
Verified Chemical & Regulatory Registry Identifiers
Mechanism of Action & Receptor Targets
Biological Pathway and Target BindingReceptor Selectivity: It was reported to work by activating the HGF/c-Met growth-factor system in the brain; the key 2014 paper describing this mechanism was retracted in 2025. [1] J Pharmacol Exp Ther, 2014 ↗
Regulatory & FDA Approval Status
Legal and Regulatory ClassificationsNot approved by the US FDA or any other regulator; it is a research compound. [1] U.S. Food and Drug Administration, 2026 ↗ [2] J Pharmacol Exp Ther, 2014 ↗
Dihexa (PNB-0408) is not approved for commercial sale, prescription therapy, or compounded medication distribution. It exists strictly within authorized scientific and clinical research frameworks.
Human Evidence & Clinical Trials
Clinical Study Readouts and Evidence SynthesesNo human clinical trial has been published. J Pharmacol Exp Ther 2014 reported pro-cognitive and synapse-forming effects dependent on the HGF/c-Met system; the journal issued an expression of concern in 2021 and retracted the paper in 2025. Brain Sci 2021: in an Alzheimer-model animal, dihexa improved performance in a water-maze memory test and reduced inflammatory markers. [1] Brain Sci, 2021 ↗ [2] J Pharmacol Exp Ther, 2014 ↗
Clinical Evidence
No human clinical trial has been published. J Pharmacol Exp Ther 2014 reported pro-cognitive and synapse-forming effects dependent on the HGF/c-Met system; the journal issued an expression of concern in 2021 and retracted the paper in 2025. Brain Sci 2021: in an Alzheimer-model animal, dihexa improved performance in a water-maze memory test and reduced inflammatory markers.
Safety Profile & Clinical Limitations
Documented Adverse Events and Known UncertaintiesThere are no human safety data. The FDA states that there are no human exposure data for dihexa and its safety issues are unknown. Activation of the HGF/c-Met growth-factor system is also involved in cell growth, which has not been studied for safety. [1] U.S. Food and Drug Administration, 2026 ↗
Effects and safety in people are unknown, and the main mechanistic paper has been retracted. [1] U.S. Food and Drug Administration, 2026 ↗ [2] J Pharmacol Exp Ther, 2014 ↗
Dose Approval Status
Commercial Dosing Status and Policy DirectivesNo dose is approved or established for humans, and no human dose-finding study has been published. [1] Brain Sci, 2021 ↗
Under Egypt Peptides medical governance policies, no personal dosages, titration intervals, cycles, stacking recommendations, or self-injection instructions may be provided for unapproved investigational compounds. Clinical study protocols represent controlled experimental research parameters exclusively.
What is Known vs. What is Unknown
Evidence Comparison and Clinical Evidence Boundaries✓ Confirmed Scientific Evidence
- Dihexa is a small modified peptide derived from angiotensin IV, studied in experimental animals for memory and cognition.
- Targets & Selectivity: It was reported to work by activating the HGF/c-Met growth-factor system in the brain; the key 2014 paper describing this mechanism was retracted in 2025.
- No human clinical trial has been published. J Pharmacol Exp Ther 2014 reported pro-cognitive and synapse-forming effects dependent on the HGF/c-Met system; the journal issued an expression of concern in 2021 and retracted the paper in 2025. Brain Sci 2021: in an Alzheimer-model animal, dihexa improved performance in a water-maze memory test and reduced inflammatory markers.
- Safety considerations: There are no human safety data. The FDA states that there are no human exposure data for dihexa and its safety issues are unknown. Activation of the HGF/c-Met growth-factor system is also involved in cell growth, which has not been studied for safety.
? Unknown / Under Ongoing Investigation
- Effects and safety in people are unknown, and the main mechanistic paper has been retracted.
Verified Questions & Answers
10 Verified scientific answers with permanent anchor keysDihexa is a small modified peptide derived from angiotensin IV, studied in experimental animals for memory and cognition.
It was reported to work by activating the HGF/c-Met growth-factor system in the brain; the key 2014 paper describing this mechanism was retracted in 2025.
No. Not approved by the US FDA or any other regulator; it is a research compound.
- Certain bulk drug substances for use in compounding that may present significant safety risks (U.S. Food and Drug Administration, 2026-04-22)
- The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the HGF/c-Met system (retracted in 2025) (J Pharmacol Exp Ther, 2014-11-01)
No human clinical trial has been published. Evidence comes only from experimental animals, and the key 2014 paper on its mechanism (J Pharmacol Exp Ther) was retracted in 2025 after an expression of concern in 2021.
No human clinical trial has been published. J Pharmacol Exp Ther 2014 reported pro-cognitive and synapse-forming effects dependent on the HGF/c-Met system; the journal issued an expression of concern in 2021 and retracted the paper in 2025. Brain Sci 2021: in an Alzheimer-model animal, dihexa improved performance in a water-maze memory test and reduced inflammatory markers.
- AngIV-analog dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via the PI3K/AKT signaling pathway (Brain Sci, 2021-10-30)
- The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the HGF/c-Met system (retracted in 2025) (J Pharmacol Exp Ther, 2014-11-01)
There are no human safety data. The FDA states that there are no human exposure data for dihexa and its safety issues are unknown. Activation of the HGF/c-Met growth-factor system is also involved in cell growth, which has not been studied for safety.
- Certain bulk drug substances for use in compounding that may present significant safety risks (U.S. Food and Drug Administration, 2026-04-22)
Effects and safety in people are unknown, and the main mechanistic paper has been retracted.
- Certain bulk drug substances for use in compounding that may present significant safety risks (U.S. Food and Drug Administration, 2026-04-22)
- The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the HGF/c-Met system (retracted in 2025) (J Pharmacol Exp Ther, 2014-11-01)
No dose is approved or established for humans, and no human dose-finding study has been published.
There is no approved product label, so no official storage instructions exist.
It is not named individually on the 2026 WADA Prohibited List. Under section S0 (non-approved substances), any pharmacological substance without a current approval by a government health authority for human therapeutic use is prohibited at all times. Athletes should confirm with their national anti-doping organisation.
- WADA Prohibited List (World Anti-Doping Agency)
Egypt Peptides publishes reviewed scientific reference monographs for documentation and research. The site does not give individual medical advice, preparation or injection instructions, combination protocols or off-label use instructions. Decisions about any medicine belong to the treating physician.
Authoritative Sources & Literature Registry
Regulatory dossiers, clinical trial registries, and published studiesCertain bulk drug substances for use in compounding that may present significant safety risks ↗
https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
AngIV-analog dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via the PI3K/AKT signaling pathway ↗
https://pubmed.ncbi.nlm.nih.gov/34827486/
The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the HGF/c-Met system (retracted in 2025) ↗
https://pubmed.ncbi.nlm.nih.gov/25187433/