Neuroscience Research

Dihexa: Angiotensin IV Analog Research Data

A conservative review of dihexa: its chemistry and origin, the research-integrity record, the developer and independent animal studies, its prodrug's failed trials, and where regulators stand in 2026.

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Fact-checked · Reviewed by Remy Research Editorial Board
Update History ▾
October 6, 2026: Initial publication, built from a source-by-source check of every primary dihexa paper, the 2025 retraction notices, FDA compounding records and the fosgonimeton trial results. It separates dihexa from its prodrug and flags which findings rest on retracted or concern-flagged work.
Research-use-only framing applied throughout in line with Remy editorial standards.
TL;DR — Research Summary

Dihexa is a small angiotensin IV-derived peptidomimetic from Washington State University, studied only in cells and animals, and the paper behind its main proposed mechanism has been retracted. Its developers reported that it reversed memory deficits in rats and proposed that it works by boosting hepatocyte growth factor (HGF) and its receptor, c-Met.[1] In 2025 the journal retracted the 2014 mechanism paper and two other papers from the lab after a university investigation found falsified or fabricated data; the 2013 paper that introduced dihexa carries an Expression of Concern.[2][3][4]

Dihexa itself has never been tested in humans, and no toxicology has been published.[5][6] Its phosphate prodrug, fosgonimeton, is a different compound that failed its primary endpoints in clinical trials.[7] Material supplied by Remy Research is for in-vitro laboratory research only — not for human or veterinary use.

Compliance note: this page is a research review, not a treatment guide. It does not provide human-use dosing, therapeutic recommendations, or any clinical-use instructions, and should be read in the same non-therapeutic frame required across Remy's research content.

What Is Dihexa?

Dihexa is a peptidomimetic: two amino acids, tyrosine and isoleucine, capped with an N-terminal hexanoyl group and a C-terminal 6-aminohexanoic amide. PubChem lists it as C27H44N4O5, with a molecular weight of about 504.7 g/mol, CAS number 1401708-83-5, and PubChem CID 129010512.[8] It was derived from angiotensin IV, and its developers described it both as a modified angiotensin IV-related peptide and as a small molecule.[1]

Origin: Washington State University

Dihexa came from Joseph Harding and John Wright's angiotensin IV work at Washington State University; the first peer-reviewed description appeared in 2012–2013, and its authors declared that they founded the company developing the technology.[1] The popular claim that dihexa is "seven orders of magnitude" more potent than BDNF comes from a 2012 university press release; the peer-reviewed paper contains no BDNF comparison.[9][1]

Fosgonimeton (ATH-1017), the clinical candidate of the company that grew out of this work, is a different molecule: dihexa with a phosphate group added, which the body converts back to dihexa. FDA's substance registry records the prodrug relationship.[10] Its trials are context, not evidence about dihexa products.

The Research-Integrity Record

Any reading of the dihexa literature has to start here. In 2021 the Journal of Pharmacology and Experimental Therapeutics issued Expressions of Concern for four papers from the developer lab, citing possible image manipulation.[4] In April 2025 it retracted three of them after a Washington State University investigation found falsified and/or fabricated data, including the 2014 paper that proposed dihexa's HGF/c-Met mechanism.[3][2] The 2013 paper that first described dihexa was not retracted, but its Expression of Concern stands.[4] A 2015 review by the developers, which presented dihexa as a first-in-class HGF/c-Met agent, drew on papers that were later retracted or flagged.[11]

Proposed Mechanisms and the Evidence Behind Each

Dihexa — Proposed Mechanisms and Evidence
Proposed mechanism What was reported Evidence and source
HGF/c-Met boost Binding to HGF and activation of the c-Met receptor Primary paper retracted; one independent rat study found a memory effect blocked by a MET antagonist
Synapse formation More dendritic spines in cultured neurons Developer papers, one retracted and one under an Expression of Concern
PI3K/AKT signalling Lower brain inflammation markers and PI3K/AKT activation in an Alzheimer's mouse model One independent group
HGF-like activity Replaced HGF in protocols that turn stem cells into liver-like cells In vitro, independent labs

The HGF-binding claim rests on the retracted 2014 paper.[2] An independent 2025 rat study gives partial support for MET dependence: a working-memory effect was blocked by a MET-antagonist peptide.[12] A Chinese group reported PI3K/AKT activation and lower inflammation in Alzheimer's model mice, and stem-cell labs have used dihexa as an HGF substitute in culture.[13][14]

The Animal Evidence: Developer and Independent

The developers reported that dihexa reversed scopolamine-induced memory deficits in rats and improved learning in aged rats, in groups of six to ten animals; that paper carries the Expression of Concern.[1][4] Developer-linked studies also reported protection of zebrafish hair cells and, combined with stem cells, motor recovery after nerve injury in rats.[15][16]

Only three independent animal studies exist, and they disagree:

The scopolamine and aged-rat results, and efficacy by the oral route, have not been independently replicated. Of 19 PubMed records for dihexa, 14 concern the compound.[18]

Fosgonimeton: the Prodrug's Trials

Fosgonimeton reached human trials, given by daily injection. In the largest, LIFT-AD, with 287 people in the primary analysis, it did not meet its primary or secondary endpoints in mild-to-moderate Alzheimer's disease, and discontinuation for adverse events was higher than on placebo.[7] Earlier phase 2 trials also missed their primary endpoints. These trials tested a different compound, formulation and route, so they are not evidence about dihexa products — but they are the only human data in this lineage, and they did not show efficacy. The sponsor's own preclinical work on the active metabolite described HGF/MET positive modulation.[19]

What Has Been Published on Safety

Regulatory Status in 2026

Where dihexa stands as of October 6, 2026.
  • United States. No FDA-approved product exists. Dihexa acetate was in Category 2 ("may present significant safety risks") from September 2023 and came off that list only because its nominations were withdrawn; it is now in none of FDA's compounding categories.[6][22] FDA plans an advisory-committee review of dihexa acetate before the end of February 2027.[23]
  • European Union. No EU authorisation was located, and no EU trials are registered.[24]
  • United Arab Emirates. No UAE registration was found.
  • Sport. Dihexa is not named on WADA's 2026 or 2027 Prohibited List. Non-approved substances (S0) and growth factor modulators (S2.3, which names HGF) are both prohibited at all times, and no anti-doping ruling on dihexa was found; athletes should ask their anti-doping organisation.[25]

What the Dihexa Literature Does Not Yet Give You

These gaps are not arguments against studying dihexa. They are arguments against overselling it.

Where Dihexa Fits in an RUO Research Catalog

For research use, dihexa belongs with the neuroscience research tools: an angiotensin IV-derived peptidomimetic for cell-culture and animal-model work on HGF/MET signalling — read alongside the integrity record above. Remy Research lists the Genovare Dihexa 25mg AQ pen, supplied for in-vitro laboratory research only. It is not framed for human use, veterinary use or treatment.

For researchers reading this page as a starting point, the most useful adjacent references on this site are the Cerebrolysin review, the Semax evidence review, the COA and HPLC purity guide, and the Dubai legality brief.

Our Research Standards

This article prioritizes primary literature, retraction and correction notices, and regulatory records, and flags which findings rest on retracted or concern-flagged work. Where human data do not exist, we say so directly. No therapeutic, human-use, or veterinary-use claim is made here. Read our editorial policy →

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Editorial Review

Editorial Board, Remy Research

The Remy Research Editorial Board reviews Remy's peptide research library, with a focus on analytical verification, clinical-trial interpretation, and compliance-safe scientific communication.

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Dihexa Research FAQ

Is dihexa a peptide?

It is best described as a peptidomimetic: two amino acids, tyrosine and isoleucine, with chemical caps on both ends, about 505 g/mol. Its developers have described it both as a modified angiotensin IV-related peptide and as a small molecule.[8][1]

Is dihexa approved?

No approval was found. There is no FDA-approved product; dihexa acetate left FDA's Category 2 safety-risk list in 2026 only because its nominations were withdrawn, and FDA plans an advisory-committee review before the end of February 2027. No EU authorisation was located.[6][23][24]

Is dihexa the same as fosgonimeton?

No. Fosgonimeton is a separate molecule — dihexa with a phosphate group added — which the body converts to dihexa. It was tested in human trials and failed its primary endpoints, and those trials do not test dihexa products.[10][7]

Has dihexa been tested in humans?

Dihexa itself has not. No trials are registered, and FDA says it has identified no human exposure data for dihexa acetate products. The only human data in this lineage come from the prodrug fosgonimeton.[5][6]

Is dihexa really "ten million times more potent than BDNF"?

That figure comes from a 2012 Washington State University press release about bench assays. The peer-reviewed paper that introduced dihexa contains no BDNF comparison, and no peer-reviewed head-to-head study was found.[9][1]

Were dihexa studies retracted?

Yes, in part. In 2025 the journal retracted three papers from the developer lab after a university investigation found falsified or fabricated data, including the 2014 paper that proposed dihexa's HGF/c-Met mechanism. The 2013 paper that introduced dihexa carries an Expression of Concern.[3][2][4]

Does dihexa carry a cancer risk?

That is unknown. Dihexa is proposed to boost HGF/c-Met signalling, and MET is a well-established cancer-driving gene, so reviewers have raised a theoretical concern. No study has tested it, and no toxicology has been published.[21][20]

Is dihexa banned in sport?

It is not named on WADA's 2026 or 2027 Prohibited List, but non-approved substances and growth factor modulators, including HGF, are prohibited at all times. Athletes should check with their anti-doping organisation.[25]

Sources

  1. McCoy AT, Benoist CC, Wright JW, et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013;344(1):141-154. doi: 10.1124/jpet.112.199497 · PMID: 23055539 ↩
  2. Benoist CC, Kawas LH, Zhu M, et al. 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. doi: 10.1124/jpet.114.218735 · PMID: 25187433 Retracted in 2025. ↩
  3. Journal of Pharmacology and Experimental Therapeutics. Retraction notices for three Harding-lab papers after a Washington State University investigation found falsified and/or fabricated data, April 2025. sciencedirect.com ↩
  4. J Pharmacol Exp Ther. Notice of Concern: McCoy AT, et al. (2013) Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2021;378(3):313. doi: 10.1124/jpet.112.199497concern · PMID: 34551989 ↩
  5. ClinicalTrials.gov search for dihexa, run October 6, 2026 (0 studies; fosgonimeton studies are listed separately). clinicaltrials.gov ↩
  6. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (dihexa acetate listed under "nominated but withdrawn"; page modified April 22, 2026). fda.gov ↩
  7. Porsteinsson AP, Sabbagh M, Tariot PN, et al. Fosgonimeton in mild-to-moderate Alzheimer's disease. J Alzheimers Dis Rep. 2025;9:25424823251405817. doi: 10.1177/25424823251405817 · PMID: 41393340 ↩
  8. National Center for Biotechnology Information. PubChem Compound Summary for CID 129010512, Dihexa. pubchem.ncbi.nlm.nih.gov/compound/129010512 ↩
  9. Washington State University News. Prospective Alzheimer's drug builds new brain cell connections (press release), October 11, 2012. archive.news.wsu.edu ↩
  10. U.S. FDA Global Substance Registration System. Fosgonimeton (UNII H91OA9858J), recorded as a prodrug whose active metabolite is dihexa (UNII 9WYX65A5C2). gsrs.ncats.nih.gov ↩
  11. 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. doi: 10.3233/JAD-142814 · PMID: 25649658 ↩
  12. Martino KA, Nakhre A, Demarest RM, et al. Hepatocyte Growth Factor/MET Activator Rescues Working Memory Deficits after Repeated Mild Traumatic Brain Injury. Neurotrauma Rep. 2025;6(1):991-998. doi: 10.1177/2689288X251392851 · PMID: 42825082 ↩
  13. Sun X, Deng Y, Fu X, et al. 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. doi: 10.3390/brainsci11111487 · PMID: 34827486 ↩
  14. Siller R, Greenhough S, Naumovska E, Sullivan GJ. Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells. Stem Cell Reports. 2015;4(5):939-952. doi: 10.1016/j.stemcr.2015.04.001 · PMID: 25937370 ↩
  15. 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. doi: 10.3389/fncel.2015.00003 · PMID: 25674052 ↩
  16. Weiss JB, Phillips CJ, Malin EW, et al. 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. doi: 10.1016/j.amsu.2021.102917 · PMID: 34703584 ↩
  17. Wells RG, Azzam AF, Hiller AL, et al. 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. doi: 10.3233/JHD-231507 · PMID: 38489193 ↩
  18. PubMed search for "dihexa", run October 6, 2026 (19 records, 14 of them about the compound). pubmed.ncbi.nlm.nih.gov ↩
  19. Johnston JL, Reda SM, Setti SE, et al. Fosgonimeton, a Novel Positive Modulator of the HGF/MET System, Promotes Neurotrophic and Procognitive Effects in Models of Dementia. Neurotherapeutics. 2023;20(2):431-451. doi: 10.1007/s13311-022-01325-5 · PMID: 36538176 ↩
  20. Alzheimer's Drug Discovery Foundation. Cognitive Vitality report: Dihexa (last updated August 13, 2021). alzdiscovery.org ↩
  21. Comoglio PM, Trusolino L, Boccaccio C. Known and novel roles of the MET oncogene in cancer: a coherent approach to targeted therapy. Nat Rev Cancer. 2018;18(6):341-358. doi: 10.1038/s41568-018-0002-y · PMID: 29674709 ↩
  22. U.S. Food and Drug Administration. Bulk drug substances nominated for use in compounding under section 503A: Categories 1–3 (updated May 14, 2026; dihexa not listed). fda.gov/media/94155 ↩
  23. U.S. Food and Drug Administration. Upcoming Pharmacy Compounding Advisory Committee meeting, before the end of February 2027 (dihexa acetate, cathelicidin LL-37, GHK-Cu, Melanotan II and PEG-MGF). fda.gov ↩
  24. EU Clinical Trials Register search for dihexa, run October 6, 2026 (0 trials). clinicaltrialsregister.eu ↩
  25. World Anti-Doping Agency. 2027 Prohibited List: dihexa is not named; S0 covers non-approved substances and S2.3 covers growth factors and growth factor modulators, naming hepatocyte growth factor. wada-ama.org ↩

For catalog details, see the Genovare Dihexa 25mg AQ pen. For compliance context, continue to the Dubai legality brief and the research standards page.

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