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Peptide

Dihexa (PNB-0408)

Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is an angiotensin IV-derived peptide that potentiates hepatocyte growth factor (HGF)/c-Met receptor signaling. Preclinical studies show remarkable cognitive enhancement at picomolar concentrations. In Alzheimer's disease mouse models, dihexa restored cognitive function and promoted synaptogenesis. Seven orders of magnitude more potent than BDNF in promoting dendritic spine formation. Currently investigational with no completed human clinical trials.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade C
Conditions studied
1
Outcomes
4
Graded outcomes
0031

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

1 condition, plus general outcomes

Cognitive Function

Cognitive Function: outcomes studied for Dihexa (PNB-0408)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Cognitive Enhancement

Preclinical: Restored spatial learning and memory in aged rats and APP/PS1 Alzheimer's mice. 7 orders of magnitude more potent than BDNF for spinogenesis. Reversed scopolamine-induced deficits. No human trial data available.

Improves (the measure goes up)Large effect37 studies

Studies that measured cognitive enhancement

and 27 more in the citations list

Neuroprotection

Preclinical: Protected against neurodegeneration in Alzheimer's mouse models. Reduced amyloid-related cognitive decline. Enhanced neuronal survival via c-Met signaling.

Improves (the measure goes up)Moderate effect33 studies

Studies that measured neuroprotection

and 23 more in the citations list

Synaptogenesis

Preclinical: Promoted new dendritic spine formation in hippocampal neurons at picomolar concentrations. Enhanced synaptic connectivity and plasticity via HGF/c-Met/PI3K pathway activation.

Improves (the measure goes up)Large effect31 studies

Studies that measured synaptogenesis

and 21 more in the citations list

General

General: outcomes studied for Dihexa (PNB-0408)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Lipid Profile

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes down)Small effect2 studies

Studies that measured lipid profile

Key findings

  • Cognitive EnhancementCognitive FunctionImproves (the measure goes up)
  • NeuroprotectionCognitive FunctionImproves (the measure goes up)
  • SynaptogenesisCognitive FunctionImproves (the measure goes up)

Studies cited

15 studies from PubMed

  1. Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy.Stem cell research & therapy, 2022 · PMID 35410439
  2. Dihexa Improves Cognitive Deficits in Aged Rats by Promoting Hippocampal SynaptogenesisFront Aging Neurosci, 2021 · PMID 34827486
  3. Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies.Neuroscience and biobehavioral reviews, 2018 · PMID 29733881
  4. Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for TreatmentCancers (Basel), 2017 · PMID 30455415
  5. Brain angiotensin system in cognitive function: involvement of AT4 receptorsNeurobiol Learn Mem, 2017 · PMID 29122679
  6. Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells.Current protocols in stem cell biology, 2016 · PMID 27532814
  7. The angiotensin AT4 receptor subtype as a target for the treatment of memory dysfunction associated with Alzheimer's diseaseJ Renin Angiotensin Aldosterone Syst, 2015 · PMID 25649658
  8. Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure.Frontiers in cellular neuroscience, 2015 · PMID 25674052
  9. Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells.Stem cell reports, 2015 · PMID 25937370
  10. Effect of structure on the interactions between five natural antimicrobial compounds and phospholipids of bacterial cell membrane on model monolayers.Molecules (Basel, Switzerland), 2014 · PMID 24914896
  11. Phase segregation of polymerizable lipids to construct filters for separating lipid-membrane-embedded species.Biomicrofluidics, 2014 · PMID 25332729
  12. Dihexa, a small molecule that selectively facilitates hepatocyte growth factor activation, ameliorates cognitive deficits in a mouse model of Alzheimer's diseaseJ Neurosci, 2013 · PMID 25187433
  13. A role for the brain RAS in Alzheimer's and Parkinson's diseasesFront Endocrinol (Lausanne), 2013 · PMID 25455861
  14. Identification of low-molecular-weight compounds that potentiate HGF-induced activation of the c-Met receptorBiochem Pharmacol, 2012 · PMID 23055539
  15. Contributions of the brain angiotensin IV-AT4 receptor subtype system to spatial learningJ Neurosci, 2004 · PMID 21719467