--- title: "Dihexa | PepTracker Pro" description: "A hexapeptide analog studied for cognitive enhancement via hepatocyte growth factor pathway activation." lang: en json-ld: | [ { "@context": "https://schema.org", "@type": "Organization", "name": "PepTracker Pro", "url": "https://peptrackerpro.com", "logo": "https://peptrackerpro.com/favicon.png", "description": "Evidence-based educational resource dedicated to improving peptide research literacy.", "contactPoint": { "@type": "ContactPoint", "email": "hello@peptrackerpro.com", "contactType": "customer support" }, "sameAs": [] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "Dihexa", "description": "A hexapeptide analog studied for cognitive enhancement via hepatocyte growth factor pathway activation.", "url": "https://peptrackerpro.com/peptides/dihexa", "lastReviewed": "2026-06-22", "reviewedBy": { "@type": "Organization", "name": "PepTracker Pro Research Team", "url": "https://peptrackerpro.com" }, "isPartOf": { "@type": "WebSite", "name": "PepTracker Pro", "url": "https://peptrackerpro.com" } }, { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://peptrackerpro.com" }, { "@type": "ListItem", "position": 2, "name": "Peptides", "item": "https://peptrackerpro.com/peptides" }, { "@type": "ListItem", "position": 3, "name": "Dihexa", "item": "https://peptrackerpro.com/peptides/dihexa" } ] }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "People researching nootropic peptides?", "acceptedAnswer": { "@type": "Answer", "text": "Dihexa is a research peptide studied in preclinical models. A hexapeptide analog studied for cognitive enhancement via hepatocyte growth factor pathway activation." } }, { "@type": "Question", "name": "Those interested in HGF/c-Met signaling?", "acceptedAnswer": { "@type": "Answer", "text": "Dihexa is a research peptide studied in preclinical models. A hexapeptide analog studied for cognitive enhancement via hepatocyte growth factor pathway activation." } }, { "@type": "Question", "name": "Individuals following cognitive enhancement research?", "acceptedAnswer": { "@type": "Answer", "text": "Dihexa is a research peptide studied in preclinical models. A hexapeptide analog studied for cognitive enhancement via hepatocyte growth factor pathway activation." } } ] } ] --- [Skip to main content](#main) **Educational information only.** This site does not provide medical advice. [Read full disclaimer](/disclaimer) [PepTracker Pro](/) [Home](/)[Peptides](/peptides)[Compare](/compare)[Glossary](/glossary)[Blog](/blog)[Calculators](/calculators)[Start Here](/start) [Open the App](https://app.peptrackerpro.com) [Peptides](/peptides)/ Dihexa **Research-only content.** This page is for educational purposes and does not constitute medical advice. [Read full disclaimer →](/research-disclaimer) # Dihexa Low Evidence A hexapeptide analog studied for cognitive enhancement via hepatocyte growth factor pathway activation. Aliases N-hexanoic-Tyr-Ile-(6) aminohexanoic amide Evidence Low Evidence Last Updated 2026-06-22 Reading Time 3 min ## Table of Contents 1. [What It Is](#what-it-is) 2. [Regulatory Status](#regulatory-status) 3. [Why Researchers Study It](#why-researchers-study) 4. [Proposed Mechanisms](#proposed-mechanisms) 5. [Evidence Snapshot](#evidence-snapshot) 6. [Commonly Discussed Benefits](#benefits) 7. [Safety & Cautions](#safety) 8. [Comparisons](#comparisons) 9. [Calculator Tools](#calculator) 10. [Citations](#citations) ## What It Is Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a synthetic hexapeptide analog derived from angiotensin IV, originally developed at Washington State University. It is one of the most potent synaptogenic compounds identified in preclinical research, with studies showing synaptogenesis amplification rates seven times greater than brain-derived neurotrophic factor (BDNF) alone. Unlike conventional nootropics that modulate neurotransmitter availability, dihexa binds to hepatocyte growth factor (HGF) receptors and activates the c-Met/PI3K/AKT signaling pathway, triggering structural changes in dendritic spine density that can persist weeks after administration stops. A 2021 study in APP/PS1 Alzheimer's model mice demonstrated that dihexa rescued cognitive impairment and recovered memory function via PI3K/AKT signaling. A 2026 study from the University of Toronto's Cognitive Neuroscience Lab, published in Neuropsychopharmacology, reported that dihexa administration at 5 mg/kg in non-human primates produced measurable increases in dendritic spine density within 14 days. Dihexa is notable for its oral bioavailability and exceptional blood-brain barrier permeability, properties uncommon among peptide compounds. As of April 2026, the FDA removed dihexa from the Category 2 bulk substances list, and it will be reviewed by the PCAC. Despite growing interest in cognitive enhancement applications, no FDA-approved human clinical trials are actively recruiting. The involvement of the HGF/c-Met pathway — which also plays a role in tumor growth and metastasis — remains a theoretical safety concern that has slowed clinical translation. Also known as: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide ## Regulatory Status Category 1 — Bulk Compounding (PCAC review before February 2027) Removed from Category 2 in the FDA's April 2026 reclassification. Dihexa is in the second PCAC session group (alongside LL-37, GHK-Cu injectable, PEG-MGF, and Melanotan II) scheduled before February 2027. No FDA-approved human clinical trials actively recruiting. Effective: April 2026 [View FDA Source](https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding) ## Why Researchers Study It Dihexa occupies a unique position in neuropeptide research because of its extraordinary potency as a synaptogenic agent and its oral bioavailability with blood-brain barrier penetration. Its mechanism via the HGF/c-Met pathway is mechanistically distinct from all other cognitive peptides, offering potential insights into structural neuroplasticity and memory formation. ## Proposed Mechanisms - Binds hepatocyte growth factor (HGF) receptors, activating the c-Met signaling cascade - Triggers PI3K/AKT pathway, promoting dendritic spine formation and synaptic connectivity - Amplifies synaptogenesis at rates reported as 7× greater than BDNF alone - Structural changes in dendritic spines persist weeks after administration ceases - Crosses blood-brain barrier with high efficiency; orally bioavailable ## Evidence Snapshot Low Evidence Low Medium High Study Type Model Outcome Link Animal (APP/PS1 mouse) Alzheimer's disease model — cognitive impairment Dihexa rescued cognitive impairment and recovered memory via PI3K/AKT signaling pathway activation [Source](https://pmc.ncbi.nlm.nih.gov/articles/PMC8615599/) Animal (rat) Scopolamine-induced memory impairment Dramatic improvements in memory acquisition and retention tasks; potency exceeding BDNF [Source](https://pubmed.ncbi.nlm.nih.gov/24444846/) Animal (non-human primate, 2026) Dendritic spine density measurement Measurable increases in dendritic spine density within 14 days at 5 mg/kg; synaptogenesis rates 7× BDNF [Source](https://www.realpeptides.co/dihexa-clinical-trials-2026-research-status-update/) ## Commonly Discussed Benefits [Cognition](/benefits/cognition)[Neuroprotection](/benefits/neuroprotection)[Anti-Aging](/benefits/anti-aging) Researching Dihexa ? Track it, set reminders, and keep notes in the free app. [Track in App](https://app.peptrackerpro.com/?add=dihexa) ## Safety & Cautions - All published efficacy data from animal models only — no human clinical trials completed - HGF/c-Met pathway involvement raises theoretical oncogenic risk concerns - Long-term safety profile completely unknown in humans - Removed from FDA Category 2 in April 2026; PCAC review scheduled before February 2027 (second session, alongside LL-37, GHK-Cu injectable, PEG-MGF, and Melanotan II) - Not FDA-approved for any condition ## Comparisons See how Dihexa compares to related peptides: [Dihexa vs CAQK](/compare/dihexa-vs-caqk) [Dihexa vs Davunetide](/compare/dihexa-vs-davunetide) [Dihexa vs P21](/compare/dihexa-vs-p21) [Dihexa vs Selank](/compare/dihexa-vs-selank) [Dihexa vs Semax](/compare/dihexa-vs-semax) [Dihexa vs Trontinemab](/compare/dihexa-vs-trontinemab) ## Calculator Tools Use our research tools to explore dosing and reconstitution data: [Reconstitution Calculator](/calculators) ## Citations 1. \[1\] Benoist CC. et al. — Dihexa, a cognitive enhancer via HGF/c-Met. J Pharmacol Exp Ther. 2014 [PubMed](https://pubmed.ncbi.nlm.nih.gov/24444846/) 2. \[2\] Wang J. et al. — Dihexa rescues cognitive impairment in APP/PS1 mice via PI3K/AKT. Int J Mol Sci. 2021 [PubMed](https://pmc.ncbi.nlm.nih.gov/articles/PMC8615599/) 3. \[3\] Dihexa Clinical Trials 2026 — Research Status Update. Real Peptides. 2026 [PubMed](https://www.realpeptides.co/dihexa-clinical-trials-2026-research-status-update/) ### Keep researching in the app - Log Dihexa to your private tracker - Set a dosing reminder - Compare it side-by-side with your stack [Open PepTracker Pro Free](https://app.peptrackerpro.com/?add=dihexa) [Browse more peptides](/peptides) ## Related Peptides ### CAQK Medium Evidence A brain-targeting tetrapeptide studied for neuroprotection and targeted drug delivery to injured brain and spinal cord tissue. [Neuroprotection](/benefits/neuroprotection)[brain-health](/benefits/brain-health)[targeted-delivery](/benefits/targeted-delivery)[Inflammation](/benefits/inflammation) [View Details](/peptides/caqk) [\+ Compare](/compare?select=caqk)[](https://app.peptrackerpro.com/?add=caqk) ### Davunetide Low Evidence An eight-amino-acid ADNP-derived peptide studied for microtubule stabilization, tau-related neuroprotection, and rare ADNP syndrome. [Cognition](/benefits/cognition)[Neuroprotection](/benefits/neuroprotection) [View Details](/peptides/davunetide) [\+ Compare](/compare?select=davunetide)[](https://app.peptrackerpro.com/?add=davunetide) ### P21 Medium Evidence An 11-amino-acid CNTF-derived peptide studied for its ability to upregulate BDNF expression and promote neurogenesis in cognitive decline models. [Cognition](/benefits/cognition)[Neuroprotection](/benefits/neuroprotection)[brain-health](/benefits/brain-health)[memory](/benefits/memory) [View Details](/peptides/p21) [\+ Compare](/compare?select=p21)[](https://app.peptrackerpro.com/?add=p21) ### Selank Medium Evidence A synthetic peptide analog of tuftsin studied for anxiolytic and nootropic properties. [Anxiety Relief](/benefits/anxiety-relief)[Mood](/benefits/mood)[Cognition](/benefits/cognition)[Neuroprotection](/benefits/neuroprotection)+1 more [View Details](/peptides/selank) [\+ Compare](/compare?select=selank)[](https://app.peptrackerpro.com/?add=selank) ### Semax Medium Evidence A synthetic peptide derived from ACTH, studied for cognitive enhancement and neuroprotective effects. [Cognition](/benefits/cognition)[Neuroprotection](/benefits/neuroprotection)[Mood](/benefits/mood)[Recovery](/benefits/recovery) [View Details](/peptides/semax) [\+ Compare](/compare?select=semax)[](https://app.peptrackerpro.com/?add=semax) ### Trontinemab Medium Evidence An investigational, brain-penetrant anti-amyloid antibody from Roche/Genentech that uses the proprietary 'Brainshuttle' transferrin-receptor delivery system to reach the brain far more efficiently than conventional antibodies. Trontinemab (development codes RG6102 / RO7126209) is a 2+1 bispecific molecule: it fuses the amyloid-beta-clearing antibody gantenerumab to a fragment that grabs transferrin receptor 1 (TfR1) on blood-brain-barrier cells, hitching a ride into the brain via the same receptor-mediated transport that carries iron. That shuttle lets a low intravenous dose clear amyloid plaques rapidly and deeply while triggering strikingly little of the brain swelling and micro-bleeding (ARIA) that limits approved anti-amyloid drugs. In the Phase Ib/IIa Brainshuttle AD study (NCT04639050), the 3.6 mg/kg dose removed roughly 107 centiloids of amyloid after 28 weeks, driving about 91-92% of participants below the amyloid-positivity threshold (24 centiloids) - with ARIA-E seen in fewer than 5% of participants, well below the ~13% reported for lecanemab and ~24% for donanemab. On the strength of those data, Roche launched two identical pivotal Phase 3 trials - TRONTIER 1 and TRONTIER 2 - in early symptomatic Alzheimer's disease (about 1,600 patients across 18 countries, begun in 2025), and at the 2026 Alzheimer's Association International Conference (AAIC) in London it unveiled PrevenTRON, a Phase 3 prevention trial in 1,600 cognitively unimpaired people at high risk (elevated plasma p-tau217). Trontinemab is a prescription-stage investigational biologic - it is not approved anywhere and is not a supplement or research chemical. [cognitive-health](/benefits/cognitive-health)[Neuroprotection](/benefits/neuroprotection)[amyloid-clearance](/benefits/amyloid-clearance)[alzheimers (investigational)]() [View Details](/peptides/trontinemab) [\+ Compare](/compare?select=trontinemab)[](https://app.peptrackerpro.com/?add=trontinemab) [PepTracker Pro](/) Educational peptide information and research tracking tools. Not medical advice. #### Explore - [Peptide Directory](/peptides) - [Compare Peptides](/compare) - [Glossary](/glossary) - [Benefits](/benefits/sleep) #### Learn - [Blog](/blog) - [Calculators](/calculators) - [Start Here](/start) - [About](/about) #### Legal - [Editorial Policy](/editorial-policy) - [Research Disclaimer](/research-disclaimer) - [Disclaimer](/disclaimer) - [Privacy Policy](/privacy) - [Terms of Service](/terms) - [Contact](/contact) © 2026 PepTracker Pro. 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