Evidence Snapshot
What this grade covers
A for chemical identity; B for selected cell and animal mechanism/cognition findings; E for human exposure, safety, efficacy, dementia treatment, neuroregeneration, cognitive enhancement, approval, or dosing.
Regulatory Context
Experimental research compound; no FDA-approved Dihexa product or verified direct human clinical trial was identified. Do not equate Dihexa with later related development compounds or prodrugs.
Research Takeaway
Dihexa is a metabolically stabilized angiotensin-IV-derived peptidomimetic developed as a procognitive/synaptogenic research compound and is distinct from angiotensin IV, Nle1-AngIV, HGF itself, fosgonimeton, and unrelated nootropic peptides.
Evidence boundary: Results for parent AngIV compounds or other HGF/c-Met modulators do not automatically transfer to Dihexa.
See all 6 evidence claims →Quick Summary
Dihexa is a metabolically stabilized angiotensin-IV-derived peptidomimetic studied for HGF/c-Met potentiation and synaptogenic effects. Evidence remains preclinical.
Mechanism & Research Overview
Dihexa binds hepatocyte growth factor and potentiates HGF-dependent c-Met signaling in experimental systems. Rodent studies report synaptogenic and cognitive effects in impairment models.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Dihexa is a metabolically stabilized angiotensin-IV-derived peptidomimetic developed as a procognitive/synaptogenic research compound and is distinct from angiotensin IV, Nle1-AngIV, HGF itself, fosgonimeton, and unrelated nootropic peptides.
Does not establish
Evidence boundary: Results for parent AngIV compounds or other HGF/c-Met modulators do not automatically transfer to Dihexa.
Supported
Preclinical work indicates that Dihexa's synaptogenic/procognitive activity depends on the hepatocyte-growth-factor/c-Met signaling system.
Does not establish
Evidence boundary: Demonstrating pathway dependence in experimental models does not establish human cognitive efficacy.
Supported
Dihexa increased dendritic-spine/synaptic measures and improved performance in animal models of cognitive impairment in the published preclinical program.
Does not establish
Evidence boundary: Animal cognitive-model results cannot be presented as evidence that Dihexa treats Alzheimer's disease, Parkinson's disease, traumatic brain injury, or normal human cognition.
Supported
The verified source set for Dihexa is preclinical; this package does not identify controlled human trials establishing efficacy, dose-response, long-term safety, or clinical benefit.
Does not establish
Evidence boundary: Human use claims from vendors, clinics, forums, or anecdotal reports are excluded from evidence grading.
Supported
Because Dihexa engages an HGF/c-Met-linked signaling mechanism associated with cell growth and survival biology, proliferative or oncogenic risk is a reasonable theoretical safety question, but direct clinical carcinogenic risk from Dihexa has not been established.
Does not establish
Evidence boundary: This is a mechanistic risk hypothesis, not evidence that Dihexa causes cancer in humans.
Supported
Dihexa should remain presented as an experimental preclinical compound rather than an established neurocognitive therapy. FDA states that it has not identified human exposure data for dihexa acetate and lacks important information needed to determine whether administration could cause harm in humans.
Does not establish
Evidence boundary: This FDA statement concerns dihexa acetate and current compounding-safety review; it does not establish that Dihexa is clinically harmful, but it reinforces that human safety and efficacy are not established.
Sources: FDA Significant Safety Risks for Certain Compounded Bulk Substances
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Higher-Priority Safety Consideration
c-Met is a receptor tyrosine kinase involved in cell growth, survival, motility, angiogenesis, development, invasion, and oncogenic signaling. Potentiating HGF/c-Met could have context-dependent proliferative or tumor-related effects; off-target or maladaptive synaptogenesis, altered excitatory signaling, seizure risk, behavioral change, or neuropsychiatric effects are additional concerns. Preclinical potency does not establish a therapeutic window.Safety Consideration
No direct human pharmacokinetic, safety, or efficacy data were verified.Safety Consideration
Long-term systemic c-Met potentiation raises theoretical tumor-growth and metastasis concerns; this has not been adequately tested for Dihexa.Safety Consideration
Dihexa must not be conflated with fosgonimeton/ATH-1017 or other related HGF-modulating compounds.Safety Consideration
Unknown angiogenic, hepatic, renal, cardiovascular, reproductive, and developmental effects; unknown interaction with cancers or premalignant lesions or with HGF/c-Met inhibitors or cancer therapy; uncertain human metabolism, distribution, accumulation, and blood-brain-barrier exposure; parent-versus-acetate identity differences; chemical impurities, stereochemical errors, degradation, mislabeled strength, sterility, and endotoxin risk; and unknown pregnancy, pediatric, and long-term safety.
Research Areas Being Studied
Research areas discussed on this page reflect the Cognitive / Neuro category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
No Human Study Findings Listed Yet
See preclinical, regulatory, and review sources below.
Study Tables by Evidence Type
Human Studies & Clinical Data
No Human Studies & Clinical Data Listed Yet
This section will be updated as sources are added.
Animal / Cell / Preclinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Dihexa and Aminoglycoside Hair-Cell Injury in Zebrafish | Dihexa has been studied in zebrafish hair-cell injury and other laboratory systems. Protective effects were model-, toxin-, dose-, and pathway-specific and were not universal; preclinical c-Met activation must not be generalized into brain repair, hearing restoration, motor-neuron repair, or tissue regeneration. | ||||
| Dihexa HGF/c-Met-Dependent Synaptogenesis and Cognition | In neuronal systems, Dihexa was associated with dendritic spine formation, synaptogenesis, and increased miniature excitatory postsynaptic current frequency, with effects blocked by HGF antagonism or c-Met suppression. These findings support an experimental HGF/c-Met-dependent mechanism and do not establish safe or beneficial human neurogenesis. | ||||
| Dihexa in APP/PS1 Alzheimer-Model Mice | Orally administered Dihexa improved performance in the APP/PS1 Alzheimer-model mouse, a model-specific finding that does not establish treatment of Alzheimer disease, mild cognitive impairment, traumatic brain injury, Parkinson disease, or healthy aging. | ||||
| Metabolically Stabilized Angiotensin IV Analogues Including Dihexa | Dihexa is a metabolically stabilized Angiotensin-IV-derived analogue distinct from native Angiotensin IV and Nle1-Angiotensin IV. Laboratory studies report that Dihexa binds HGF and potentiates HGF-dependent c-Met activation. |
Regulatory Documents & Official Trial Registries
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| ClinicalTrials.gov Search Portal | General trial-registry search portal used as part of this review's regulatory/trial-landscape check. | ||||
| FDA Drug Approvals and Databases | No FDA-approved Orexin A or Orexin B peptide drug or indication was identified in the reviewed FDA drug databases. | ||||
| FDA GSRS/UNII Dihexa Record | An FDA GSRS/UNII identity record is a substance-identification record, not drug approval. | ||||
| FDA PCAC Page Listing Planned Dihexa Acetate Review | FDA announced that Dihexa acetate is among substances intended for discussion by the Pharmacy Compounding Advisory Committee for possible 503A-list inclusion. Advisory review or nomination is not FDA approval, and no final favorable FDA determination was identified as of the research cutoff. | ||||
| FDA Significant Safety Risks for Certain Compounded Bulk Substances | FDA states that it has not identified human exposure data for drug products containing Dihexa acetate administered by any route and lacks important information needed to determine whether it would harm humans. | ||||
| PubChem Dihexa Record | Dihexa, also called PNB-0408, is the metabolically stabilized Angiotensin-IV-derived analogue N-hexanoic-Tyr-Ile-(6-aminohexanoic amide) -- a small peptidomimetic/oligopeptide-derived molecule rather than a native endogenous peptide, distinct from Angiotensin IV, HGF, c-Met, HGF/c-Met agonist antibodies, fosgonimeton, and other unrelated compounds. |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published and official research and does not provide medical advice, a recommendation, or instructions for human use.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-07-30.
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