Dihexa
Also known as: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, PNB-0408
Dihexa is a potent experimental oligopeptide derived from angiotensin IV that dramatically enhances synaptogenesis. Preclinical research shows cognitive enhancement orders of magnitude more potent than BDNF — it is considered one of the most powerful nootropic compounds in research, but has very limited human safety data.
Half-Life
Unknown (limited pharmacokinetic data)
Route
Oral, SubQ, Topical
Category
Cognitive Enhancement
Studies
18 references
Key Benefits
- Dramatically increases synapse formation (potentially 10 million× more potent than BDNF in animal models)
- Enhances memory and learning
- May reverse cognitive decline
- Improves neuroplasticity and executive function
- Long-lasting cognitive benefits from short courses
- Potential therapeutic agent for Alzheimer's
Mechanism of Action
Dihexa binds to hepatocyte growth factor (HGF) and potentiates its activity at c-Met receptors. This leads to dramatically enhanced synaptogenesis (formation of new synapses), increased dendritic spine density, and improved neuroplasticity. The HGF/c-Met pathway is critical for brain development, learning, and memory consolidation. Animal studies show cognitive improvements orders of magnitude more potent than BDNF.
Dosing Protocols
Experimental Protocol
- Dose
- 5–10 mg
- Frequency
- Daily
- Timing
- Morning
- Cycle
- 2–4 weeks on, 2–4 weeks off
Extremely potent — start at lowest effective dose. Very limited human safety data. Topical application also investigated due to skin permeability. Cycles with breaks strongly recommended given unknown long-term profile.
Calculate your draw volume
Enter your vial size and BAC water to get exact injection volumes
Side Effects
- Headache
- Irritability
- Brain fog during washout period
- Unknown long-term effects (insufficient data)
Contraindications
Experimental compound — limited human safety data. History of cancer (HGF/c-Met pathway theoretical concern). Pregnancy or breastfeeding. Mental health conditions.
Storage
Store at −20°C. Protect from light.
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Clinical Research
- 1.Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions
Rahman OF, Lee SJ, Seeds WA · Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2026ReviewPubMed Verified
- 2.Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats
Wells RG, Azzam AF, Hiller AL, Sardinia MF · Journal of Huntington's disease · 2024PubMed Verified
- 3.Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy
Pan T, Wang N, Zhang J, Yang F, Chen Y, Zhuang Y et al. · Stem cell research & therapy · 2022PubMed Verified
- 4.AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
Sun X, Deng Y, Fu X, Wang S, Duan R, Zhang Y · Brain sciences · 2021PubMed Verified
- 5.Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model: Experimental animal studies
Weiss JB, Phillips CJ, Malin EW, Gorantla VS, Harding JW, Salgar SK · Annals of medicine and surgery (2012) · 2021PubMed Verified
- 6.Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies
Ho JK, Nation DA · Neuroscience and biobehavioral reviews · 2018Meta-AnalysisPubMed Verified
- 7.Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells
Mathapati S, Siller R, Impellizzeri AA, Lycke M, Vegheim K, Almaas R et al. · Current protocols in stem cell biology · 2016PubMed Verified
- 8.Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells
Siller R, Greenhough S, Naumovska E, Sullivan GJ · Stem cell reports · 2015PubMed Verified
- 9.Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure
Uribe PM, Kawas LH, Harding JW, Coffin AB · Frontiers in cellular neuroscience · 2015PubMed Verified
- 10.The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease
Wright JW, Harding JW · Journal of Alzheimer's disease : JAD · 2015ReviewPubMed Verified
- 11.The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases
Wright JW, Kawas LH, Harding JW · Progress in neurobiology · 2015ReviewPubMed Verified
- 12.Phase segregation of polymerizable lipids to construct filters for separating lipid-membrane-embedded species
Hu SK, Chen YM, Chao L · Biomicrofluidics · 2014PubMed Verified
- 13.The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system
Benoist CC, Kawas LH, Zhu M, Tyson KA, Stillmaker L, Appleyard SM et al. · The Journal of pharmacology and experimental therapeutics · 2014PubMed Verified
- 14.Effect of structure on the interactions between five natural antimicrobial compounds and phospholipids of bacterial cell membrane on model monolayers
Nowotarska SW, Nowotarski KJ, Friedman M, Situ C · Molecules (Basel, Switzerland) · 2014PubMed Verified
- 15.Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents
McCoy AT, Benoist CC, Wright JW, Kawas LH, Bule-Ghogare JM, Zhu M et al. · The Journal of pharmacology and experimental therapeutics · 2013PubMed Verified
- 16.Dimeric DOTA-alpha-melanocyte-stimulating hormone analogs: synthesis and in vivo characteristics of radiopeptides with high in vitro activity
Bapst JP, Froidevaux S, Calame M, Tanner H, Eberle AN · Journal of receptor and signal transduction research · 2007PubMed Verified
- 17.Studies on the subcellular localization of the porphycene CPO
Kessel D, Conley M, Vicente MG, Reiners JJ · Photochemistry and photobiology · 2005PubMed Verified
- 18.Localization of alveolar surfactant clearance in rabbit lung cells
Rider ED, Ikegami M, Jobe AH · The American journal of physiology · 1992PubMed Verified
Medical disclaimer: This information is for educational purposes only and does not constitute medical advice. Many compounds listed are research chemicals not approved for human use. Always consult a qualified healthcare professional before starting any protocol.
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