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Peptide derived compoundMostly animalNot FDA approved

Dihexa

Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide)

Last reviewed October 27, 2026 · 21 sources · Written for general readers · Compare with another compound →

The bottom line

Dihexa has only been studied in animals and cells, and one of its key papers was retracted in 2025. Every claim about memory, Alzheimer's or brain repair comes from rodents or fish, and FDA says it has found no data on people taking it. It is not an approved drug, and FDA plans to ask its expert advisers about it before the end of February 2027.

Where the evidence stands

What it is

Dihexa is a lab made compound developed from angiotensin IV, a small fragment of a blood pressure hormone. It is built around two amino acids, tyrosine and isoleucine, with chemical groups added to each end so the body breaks it down more slowly.[1][2]

Researchers designed it as a possible Alzheimer's drug. In rats, it worked when taken by mouth and reached the brain.[2] Its developers later promoted the brain's HGF system as a new Alzheimer's target, but they described only animal results.[3] FDA says it has not found any data on people exposed to dihexa products.[4] A 2026 review of peptides noted that clinical trials of dihexa are lacking.[5]

Name
Dihexa (Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide))
Other names
PNB-0408, dihexa acetate
Type
Peptide derived compound
CAS number
1401708-83-5
Formula
C27H44N4O5
Molecular weight
About 504.7 g/mol

What it does in the body

Dihexa is not made by the body. It was built from angiotensin IV, a breakdown piece of the blood pressure hormone angiotensin.[2] Its developers say its main action is boosting hepatocyte growth factor (HGF), a natural repair signal, and its receptor c-Met, which help cells grow, move and form connections.[3][6]

This is the biology, area by area. A change measured in the body, like a higher blood level, does not always mean a person feels a benefit. The claims check below covers that.

Brain and memory

Seen in animals

In rats with drug induced memory loss and in old rats, dihexa improved water maze memory and increased new connections between brain cells.[2] In Alzheimer model mice, three months of treatment improved maze learning and lowered signs of brain inflammation.[7] In rats with repeated mild head injuries, its memory benefit disappeared when c-Met was blocked.[8]

Growth signals in human cells

Lab finding

In lab dishes, researchers have used dihexa in place of HGF to help push human stem cells to become liver like cells, which shows it can act like an HGF signal in human cells.[9][10] This was a lab tool use, not a treatment.

Hearing

Seen in animals

In zebrafish larvae, dihexa protected the sound sensing hair cells from damaging antibiotics, and a drug that blocks HGF weakened that protection.[11]

Nerves and movement

Seen in animals

In rats with a cut and repaired leg nerve, dihexa injected into the muscle together with stem cells improved movement recovery over 16 weeks.[12] In rats with a toxin model of Huntington's disease, it did not protect against weight loss, memory or movement problems.[13]

How it works

Its developers say dihexa acts like hepatocyte growth factor (HGF), a natural growth signal, by boosting HGF's receptor, called c-Met.[3]

  • In zebrafish, dihexa protected ear hair cells from damaging antibiotics, and a drug that blocks HGF weakened that protection.[11]
  • In rats with head injuries, a drug that blocks c-Met cancelled dihexa's memory benefit.[8]
  • In mice bred to develop Alzheimer like changes, dihexa switched on a cell survival pathway called PI3K/AKT.[7]
  • In human stem cell cultures, it can stand in for HGF, which supports the idea that it mimics HGF signaling.[9]
  • A key 2014 paper tying dihexa's memory effects to HGF and c-Met received an expression of concern, a formal journal warning, in 2021 and was retracted in 2025.[14]
  • The c-Met signal it targets helps cells grow and move, and it can be abnormally switched on in many human cancers.[6]

These ideas come from cell and animal work, and a central paper behind them was retracted.

What the research shows

We keep animal and human evidence apart. A result in animals is a reason to study something in people, not proof that it works in people.

Animal and lab studies

Mixed results in rats, mice and fish

  • In rats with drug induced memory loss and in old rats, dihexa improved performance in a water maze, a swimming memory test, and increased new connections between brain cells.[2]
  • In Alzheimer model mice treated for three months, dihexa improved maze learning, raised markers of nerve cells and synapses, and lowered signs of brain inflammation.[7]
  • In a study of 52 rats, some with repeated mild head injuries, dihexa infused straight into the brain raised a working memory score from about 67% to about 82% correct, and a c-Met blocker erased the gain.[8]
  • A 2018 systematic review of animal studies found that 8 of 9 studies in models with memory problems reported benefits for angiotensin IV and related compounds, a group that includes dihexa.[15]
  • A 2015 review by its developers says it showed promise against memory and movement problems in animal models of Alzheimer's and Parkinson's disease.[16]
  • In rats with a cut and repaired leg nerve, dihexa injected into the muscle together with stem cells improved movement recovery over 16 weeks. The study included one of dihexa's developers.[12]
  • In a study of 40 rats with a toxin model of Huntington's disease, dihexa did not protect against weight loss, memory problems or movement problems.[13]
  • In zebrafish larvae, it protected ear hair cells from antibiotic damage.[11]

Limit: Much of the early positive work came from the group that developed dihexa, and two of its key papers carry journal warnings, one now retracted.[2][14]

Human studies

No human studies

  • We found no published study of dihexa in people, so there is no information on what people feel, how long effects last, or what side effects occur. FDA says it has not identified any human exposure data for dihexa products and does not know whether dihexa would cause harm in humans.[4] A 2026 review also describes clinical trials as lacking.[5]

Limit: Nothing is known about what dihexa does in people, good or bad.

Claims check

The most common claims about this compound, and what studies actually found. Verdicts rate the evidence, not whether you should use it.

Boosts memory and learning

Only in animals

In rats with drug induced memory loss and in old rats, dihexa improved water maze memory.[2] That paper carries a journal expression of concern, and a 2014 follow up paper was retracted.[14] No study has tested memory in people.

Treats or prevents Alzheimer's

Only in animals

In mice bred to develop Alzheimer like changes, three months of dihexa improved maze learning and lowered brain inflammation.[7] No human trial in Alzheimer's or any other condition has been published.[4]

Helps recovery from concussion

Only in animals

In a study of 52 rats, some with repeated mild head injuries, dihexa infused into the brain restored working memory scores to about 82% correct, versus about 67% without it.[8] The drug was infused directly into the brain, and no human study exists.

Grows new brain connections

Only in animals

Rat and cell studies by its developers reported more new connections between brain cells.[2] The paper linking this to the HGF system was retracted in 2025.[14]

Repairs nerves

Only in animals

In rats with a repaired leg nerve, dihexa plus stem cells improved movement recovery over 16 weeks.[12] Dihexa did not protect rats in a Huntington's disease model.[13] There are no human data.

Helps Parkinson's disease

Only in animals

Its developers report promise against movement problems in animal models of Parkinson's disease.[16] No study has tested it in people with Parkinson's.

Protects hearing

Only in animals

In zebrafish larvae, dihexa protected sound sensing hair cells from antibiotic damage.[11] We found no study testing this in mammals or in people.

Known risks and side effects

  • Unknown effects in people. No side effects have been recorded because no one has studied dihexa in people. FDA says it lacks important safety information and does not know whether it would harm people.[4]
  • Growth signal concerns. Dihexa is meant to boost the c-Met growth signal, which is abnormally active in many cancers. Whether that matters in people has never been studied.[6][4]
  • Shaky research base. A key 2014 dihexa study was retracted, and the 2013 study that introduced it carries an expression of concern.[2][14]
  • Unregulated products. There is no approved dihexa product or US drug label, so anything sold online has had no FDA check of identity, purity or strength.[17]
  • Sport rules. WADA does not name dihexa, but its 2026 and 2027 lists ban HGF, other growth factor modulators, and any drug with no government approval for human use.[18][19]

Regulatory status

Today: Dihexa is not an approved drug and has no US drug label.[17] FDA's compounding safety page lists dihexa acetate among substances that were in Category 2, FDA's group of substances with significant safety risks, until their nominations were withdrawn.[4] FDA plans to ask its Pharmacy Compounding Advisory Committee about dihexa acetate at a meeting before the end of February 2027, and HHS's October 2026 interim compounding policy does not include it.[20][21]

  1. Researchers describe dihexa as an oral compound that reaches the brain and improves memory in rats.[2]
  2. The journal issues expressions of concern on the 2013 and 2014 dihexa papers.[2][14]
  3. The 2014 paper linking dihexa to the HGF and c-Met system is retracted.[14]
  4. FDA lists dihexa acetate as a withdrawn nomination that is no longer in Category 2, and names it for a future advisory committee meeting.[4][20]
  5. HHS files an interim policy easing enforcement for six compounded peptides. Dihexa is not on its list.[21]
  6. The 2027 WADA list takes effect. It does not name dihexa but still bans HGF, growth factor modulators and unapproved substances.[19]
  7. Planned FDA advisory committee meeting on dihexa acetate and four other peptides.[20]

Sources

  1. U.S. FDA Global Substance Registration System. Dihexa (UNII 9WYX65A5C2). Codes: CAS 1401708-83-5; PubChem CID 129010512. FDA GSRS
  2. McCoy AT, Benoist CC, Wright JW, Kawas LH, Bule-Ghogare JM, Zhu M, Appleyard SM, Wayman GA, Harding JW. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013;344(1):141-154. Expression of concern issued September 2021. PMID 23055539
  3. Wright JW, Harding JW. The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease. J Alzheimers Dis. 2015;45(4):985-1000. PMID 25649658
  4. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks. Content current as of April 22, 2026. FDA
  5. Rahman OF, Lee SJ, Seeds WA. Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions. J Am Acad Orthop Surg Glob Res Rev. 2026;10(1):e25.00236. PMID 41490200
  6. Organ SL, Tsao MS. An overview of the c-MET signaling pathway. Ther Adv Med Oncol. 2011;3(1 Suppl):S7-S19. PMID 22128289
  7. Sun X, Deng Y, Fu X, Wang S, Duan R, Zhang Y. AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway. Brain Sci. 2021;11(11):1487. PMID 34827486
  8. Martino KA, Nakhre A, Demarest RM, Devilbiss DM. Hepatocyte Growth Factor/MET Activator Rescues Working Memory Deficits after Repeated Mild Traumatic Brain Injury. Neurotrauma Rep. 2025;6(1):991-998. PMID 42825082
  9. Mathapati S, Siller R, Impellizzeri AAR, Lycke M, Vegheim K, Almaas R, et al. Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells. Curr Protoc Stem Cell Biol. 2016;38:1G.6.1-1G.6.18. PMID 27532814
  10. Pan T, Wang N, Zhang J, Yang F, Chen Y, Zhuang Y, et al. Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy. Stem Cell Res Ther. 2022;13(1):159. PMID 35410439
  11. Uribe PM, Kawas LH, Harding JW, Coffin AB. Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure. Front Cell Neurosci. 2015;9:3. PMID 25674052
  12. Weiss JB, Phillips CJ, Malin EW, Gorantla VS, Harding JW, Salgar SK. 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. Ann Med Surg (Lond). 2021;71:102917. PMID 34703584
  13. Wells RG, Azzam AF, Hiller AL, Sardinia MF. Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats. J Huntingtons Dis. 2024;13(1):55-66. PMID 38489193
  14. Benoist CC, Kawas LH, Zhu M, Tyson KA, Stillmaker L, Appleyard SM, Wright JW, Wayman GA, Harding JW. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system. J Pharmacol Exp Ther. 2014;351(2):390-402. Expression of concern 2021; retracted 2025 (J Pharmacol Exp Ther. 2025;392(4):103567). PMID 25187433 (retracted)
  15. Ho JK, Nation DA. Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies. Neurosci Biobehav Rev. 2018;92:209-225. PMID 29733881
  16. Wright JW, Kawas LH, Harding JW. The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases. Prog Neurobiol. 2015;125:26-46. PMID 25455861
  17. DailyMed. Search results for dihexa. U.S. National Library of Medicine. Searched October 2026; 0 results. DailyMed
  18. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. In force January 1, 2026. WADA 2026 List
  19. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2027. Approved September 10, 2026; in force January 1, 2027. WADA 2027 List
  20. U.S. Food and Drug Administration. Meeting of the Pharmacy Compounding Advisory Committee (meeting planned before the end of February 2027). Content current as of April 15, 2026. FDA
  21. U.S. Department of Health and Human Services. HHS Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances: appendices listing covered peptides, salt forms and routes. October 2026. HHS policy appendix
Medical disclaimer

This page is educational information only. It is not medical advice and does not replace care from a licensed medical provider. Do not use this page to decide whether to take any substance. Talk to a licensed medical provider first.

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