Dihexa
N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide, PNB-0408
REC PPT-DIHEXA // REV 2026-10-04 // assessment changes are logged, never silent
An angiotensin IV analog studied only in animals, whose two foundational mechanism papers were retracted in 2025 after a university investigation found falsified or fabricated data, and whose famous potency figure originated in a university press release rather than a cognition study.
What it is
A metabolically stabilised derivative of the tripeptide core of angiotensin IV, chemically N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide, developed at Washington State University. It is described as binding hepatocyte growth factor and modulating signalling through the receptor c-Met.
What it does
Studied in rodents for spatial-memory performance after scopolamine and in aged animals, for dendritic-spine formation in cultured hippocampal neurons, and in scattered single models of Parkinsonian injury, Huntington-like symptoms and peripheral-nerve repair. There is no human study of dihexa itself.
Does it work?
Europe PMC returns 91 records for the term but only 18 name dihexa in a title or abstract, and ClinicalTrials.gov holds no registered study of the compound. Two of the founding papers — Kawas and colleagues in the Journal of Pharmacology and Experimental Therapeutics in 2012, and Benoist and colleagues in the same journal in 2014, the paper that established the hepatocyte growth factor and c-Met mechanism — were retracted in April 2025 after a Washington State University investigation reported that figures and subsequent erratum data contained falsified or fabricated material. The closest thing to a human test of this mechanism was fosgonimeton, a dihexa prodrug developed by Athira Pharma, which missed its primary endpoint and its key secondary endpoints in the 315-participant LIFT-AD study in mild-to-moderate Alzheimer disease; the same company agreed in January 2025 to pay about 4.07 million US dollars to settle False Claims Act allegations that it failed to disclose research-misconduct allegations to the National Institutes of Health. What remains is a preclinical literature whose central mechanistic pillar has been withdrawn.
Claims vs data
Each marketing claim, tagged by what the evidence actually supports.
| Increases dendritic spine formation in cultured hippocampal neurons | preclinical only |
| Improves maze performance in scopolamine-treated and aged rodents | animal data only |
| Works by potentiating hepatocyte growth factor at c-Met | weak evidence |
| Seven orders of magnitude more potent than BDNF, and so improves cognition in humans | overreach |
Reference figures
Quoted from published reference material. These are not Peptuity recommendations.
molecular data — PubChem CID 129010512
The evidence, counted
Live counts from Europe PMC and ClinicalTrials.gov.
93 publications indexed, 0 registered interventional studies, no randomised controlled trials indexed. Evidence is minimal.
SRC // EUROPE PMC + CTGOV // "Dihexa" // FETCHED 2026-10-04 // 93 RECORDS
Most-cited literature
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[01]
Essential role of PDK1 in regulating cell size and development in mice
Lawlor MA, Mora A, Ashby PR, Williams MR, Murray-Tait V, Malone L, Pre · EMBO J 2002 · 254 citations · DOI 10.1093/emboj/cdf387
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[02]
Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid
Heyes MP, Saito K, Markey SP. · Biochem J 1992 · 165 citations · DOI 10.1042/bj2830633
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[03]
The ganglionic eminence may be an intermediate target for corticofugal and thalamocortical axons
Métin C, Godement P. · J Neurosci 1996 · 160 citations · DOI 10.1523/jneurosci.16-10-03219.1996
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[04]
Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells
Siller R, Greenhough S, Naumovska E, Sullivan GJ. · Stem Cell Reports 2015 · 158 citations · DOI 10.1016/j.stemcr.2015.04.001
Regulatory status
Formal, dated regulatory actions.
WADA — Prohibited List 2026
Prohibited in sport — WADA S0 (substance without any health-authority approval)
Common questions
Where does the ten-million-times-stronger-than-BDNF figure come from?
From an in-vitro comparison of the concentrations needed to trigger dendritic-spine formation in cultured hippocampal neurons, popularised by a 2012 Washington State University press release. It is a potency ratio in a dish for one structural endpoint, not a measurement of memory, cognition or any clinical outcome, and it says nothing about what happens in a living human brain.
Which dihexa papers were retracted, and why?
Two papers in the Journal of Pharmacology and Experimental Therapeutics: Development of Angiotensin IV Analogs as Hepatocyte Growth Factor and Met Modifiers, from 2012, and The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor and c-Met System, from 2014. Both retraction notices were published in April 2025 and state that a Washington State University investigation found figures containing falsified or fabricated data.
Did the retractions mean the whole idea was disproved?
No. A retraction removes evidence rather than replacing it with contrary evidence. What it does mean is that the two papers most often cited to explain how dihexa works can no longer be used to support that explanation, and no independent replacement has taken their place. The separate clinical failure of the dihexa prodrug fosgonimeton in Alzheimer disease also did not support the mechanism.
Is dihexa approved, and where does it stand in sport?
It is not approved by the FDA, the Saudi FDA, the EMA or any other regulator, for any indication. Because it has no human therapeutic approval anywhere, it falls inside the WADA S0 category of non-approved substances, prohibited at all times in and out of competition.
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