Dihexa

Dihexa at a Glance

Dihexa is a small synthetic tripeptide derived from angiotensin IV, designed to be orally active and to cross the blood-brain barrier — properties most neuroactive peptides lack. It works by potentiating hepatocyte growth factor signalling at its receptor, which drives the formation of new synapses. Rodent work reports potent synaptogenic and cognitive effects, and that preclinical record is the entirety of its evidence. It is an unapproved research chemical with no human data.

History & Development

Dihexa was engineered for a specific and difficult goal: a tripeptide that survives being swallowed and reaches the brain.

First described	Not established in the sources consulted for this section
Discovered / synthesised by	Not established in the sources consulted for this section
Institution	Not established in the sources consulted for this section
Origin	Small synthetic tripeptide derived from angiotensin IV, designed for oral activity and blood-brain-barrier penetration
Key patent	Not established in the sources consulted for this section
Assignee	Not established in the sources consulted for this section
Development status	Research chemical - no human data; never approved

Discovery

The brain has its own angiotensin system, distinct from the blood-pressure one. Angiotensin IV acts at the AT4 site and has procognitive effects, but it is a peptide with the usual problems - degraded quickly, poor brain access.

Dihexa is a heavily modified tripeptide derived from it, built to be orally active and to cross the blood-brain barrier. Its proposed mechanism is positive modulation of HGF/c-Met signalling, driving hippocampal spinogenesis and synaptogenesis through PI3K/AKT - building new synapses rather than adjusting the activity of existing ones.

That is a genuinely different claim from most nootropics, and it is why the compound attracted attention: reported potency in rodent synaptogenesis assays was very high.

Development & ownership

There is no human data of any kind - no trial, no pharmacokinetics, no safety study. The evidence is rodent, and the compound has not entered formal development.

The mechanism cuts both ways and the page should say so plainly. HGF/c-Met is a growth-factor pathway implicated in tumour biology, and a compound designed to potentiate it systemically, orally and across the blood-brain barrier has an obvious theoretical concern that no study has addressed.

How it reached the market

Dihexa is sold as an oral nootropic for cognition and neurogenesis, on rodent synaptogenesis data. Its oral activity - the feature that makes it convenient - is precisely what makes it easy to take casually, and nothing about its long-term effects in a person has been measured.

What It's Used For

Dihexa (PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a small, metabolically stabilized analogue of angiotensin IV — a three-residue core, Tyr-Ile plus an aminohexanoic tail, capped at both ends to resist peptidases and to raise hydrophobicity enough to cross the gut wall and the blood-brain barrier ^{1,3Reference 1McCoy AT et al. · 2013AnimalEvaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — animal (rat). [Expression of Concern, 2021 — see ref 17]View study →Reference 3Benoist CC et al. · 2011AnimalFacilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs — animal (rat)View study →}.

At ~505 Da it sits at the boundary between a peptide and a peptidomimetic small molecule. Its proposed action is not direct BDNF agonism, despite the potency comparison the internet repeats: dihexa is described as a positive modulator of the hepatocyte growth factor (HGF) / c-Met system, binding HGF and lowering the threshold at which endogenous HGF activates its receptor, which in turn drives dendritic spine formation and synaptogenesis ^{2,7,9Reference 2Benoist CC et al. · 2014In vitroThe procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-Met system — animal (rat) / in vitro. [RETRACTED 2025 — retraction notice PMID 40312093]View study →Reference 7Uribe PM et al. · 2015Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure — animal (zebrafish)View study →Reference 9Wright JW · 2015ReviewThe brain hepatocyte growth factor/c-Met receptor system: a new target for the treatment of Alzheimer’s disease — reviewView study →}.

Two facts frame everything below, and neither is optional. First, this is a single-program compound. Dihexa was designed, named, characterized and mechanistically explained by one research group — Joseph Harding and John Wright’s laboratory at Washington State University, and the spin-out (M3 Biotechnology, later Athira Pharma) built around it. That concentration is not disqualifying on its own; the same pattern applies to BPC-157. Second, and unlike BPC-157, part of that single program’s foundational output has been withdrawn for falsified data. Washington State University revoked the PhD of co-author Leen Kawas after finding she had altered images in her 2011 dissertation and in several co-authored papers; she resigned as CEO of Athira Pharma in October 2021, and Athira later paid over $4 million to settle US False Claims Act allegations that it failed to disclose the misconduct in NIH grant applications (reported by STAT, the Seattle Times and GeekWire, 2021–2024). Three of the program’s papers were retracted in 2025 ^{2,11,12Reference 2Benoist CC et al. · 2014In vitroThe procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-Met system — animal (rat) / in vitro. [RETRACTED 2025 — retraction notice PMID 40312093]View study →Reference 11Kawas LH et al. · 2012In vitroDevelopment of angiotensin IV analogs as hepatocyte growth factor/Met modifiers — in vitro. [RETRACTED 2025 — retraction notice PMID 40312092]View study →Reference 12Kawas LH et al. · 2011In vitroMimics of the dimerization domain of hepatocyte growth factor exhibit anti-Met and anticancer activity — in vitro. [RETRACTED 2025 — retraction notice PMID 40312094]View study →} and the 2013 paper that introduced dihexa carries a formal Expression of Concern ^{1,17Reference 1McCoy AT et al. · 2013AnimalEvaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — animal (rat). [Expression of Concern, 2021 — see ref 17]View study →Reference 17American Society for Pharmacology et al. · 2021Notice of Concern: McCoy AT, et al. (2013), Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — expression of concernView study →}.

What survives is thinner than the reputation. There is no human data of any kind — no trial of dihexa has ever been registered on ClinicalTrials.gov or published, and no human pharmacokinetics exist. Independent replication is genuinely limited to two mammalian studies pointing in opposite directions: an independent Chinese group reported that oral dihexa restored spatial learning in APP/PS1 Alzheimer’s-model mice via PI3K/AKT ^{4Reference 4Sun X et al. · 2021AnimalAngIV-analog dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via the PI3K/AKT signaling pathway — animal (mouse), independent groupView study →}, while an independent US group testing it in a rat Huntington’s model found no protection at all ^{6Reference 6Wells RG et al. · 2024AnimalEffects of an angiotensin IV analog on 3-nitropropionic acid-induced Huntington’s disease-like symptoms in rats — animal (rat), negative result, independent groupView study →}.

The clinical descendant of the same HGF/MET thesis, fosgonimeton, was tested properly in humans and missed its primary and every secondary endpoint in a Phase 2/3 Alzheimer’s trial ^{16Reference 16Porsteinsson AP et al. · 2025RCTFosgonimeton in mild-to-moderate Alzheimer’s disease (LIFT-AD) — human (Phase 2/3 RCT), missed primary and all secondary endpoints; fosgonimeton, not dihexaView study →} — a negative human read on the mechanism, though on a different molecule.

Evidence by IndicationStrength of support · Beta

Support is an experimental score I’m building — a composite weighted by study type (human > animal > in vitro > review) and study volume. It’s a beta: a fast way to rank strength of evidence at a glance, not a validated metric. Every score here is capped hard, for three separate reasons that compound: there is zero human data; the foundational studies are single-lab and partly retracted or under an Expression of Concern; and where independent groups have looked, the results split. Read row 4 carefully — it is low because dihexa was tested and did not work, which is a different and stronger fact than “not yet studied.” Each application links down to its write-up.

01Cognition & anti-dementiaShaky26%Origin rat models (Expression of Concern) + one independent APP/PS1 mouse study. No human data; the human test of the same mechanism, via a different molecule, failed.

02Peripheral nerve regenerationShaky16%One rat sciatic-nerve transection-repair study; benefit appeared only in a combination arm with stem cells, not dihexa alone.

03Ototoxicity / hair-cell protectionShaky14%Zebrafish lateral-line model only. A mechanism demonstration, not a hearing-protection claim.

04Huntington’s-type neuroprotectionShaky8%Negative. One independent rat 3-NP study found no protection on any measured endpoint.

Mechanisms

Note on provenance: the HGF/c-Met dependence was argued most directly in Benoist 2014, which has since been retracted ^{2Reference 2Benoist CC et al. · 2014In vitroThe procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-Met system — animal (rat) / in vitro. [RETRACTED 2025 — retraction notice PMID 40312093]View study →}. The pathway is separately supported by the zebrafish antagonist/inhibitor experiments ^{7Reference 7Uribe PM et al. · 2015Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure — animal (zebrafish)View study →} and, downstream, by the independent APP/PS1 mouse study ^{4Reference 4Sun X et al. · 2021AnimalAngIV-analog dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via the PI3K/AKT signaling pathway — animal (mouse), independent groupView study →} — so the mechanism is not left with nothing, but its strongest single demonstration is gone.

Pharmacokinetics

Route is the genuinely distinguishing feature of this compound, and it is a design achievement with a demonstration gap. Unlike the injectable neuropeptides it shares a hub with, dihexa was engineered specifically to be orally active and blood-brain-barrier permeant: the N-hexanoyl cap and C-terminal 6-aminohexanoic amide were added to the Nle-Tyr-Ile core to increase hydrophobicity, reduce hydrogen-bond donors, and resist metabolic degradation ^{1,3,10Reference 1McCoy AT et al. · 2013AnimalEvaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — animal (rat). [Expression of Concern, 2021 — see ref 17]View study →Reference 3Benoist CC et al. · 2011AnimalFacilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs — animal (rat)View study →Reference 10Wright JW et al. · 2015ReviewThe development of small molecule angiotensin IV analogs to treat Alzheimer’s and Parkinson’s diseases — reviewView study →}. At ~505 Da it is small enough for this to be plausible, which is not true of most peptides here.

What the evidence actually shows is narrower than the design intent. Oral activity has been demonstrated in rodents only — orally dosed rats in the origin study ^{1Reference 1McCoy AT et al. · 2013AnimalEvaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — animal (rat). [Expression of Concern, 2021 — see ref 17]View study →} and orally dosed APP/PS1 mice in the independent replication ^{4Reference 4Sun X et al. · 2021AnimalAngIV-analog dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via the PI3K/AKT signaling pathway — animal (mouse), independent groupView study →}, both inferred from behavioral and tissue outcomes rather than from measured plasma and brain concentrations in those reports. The claim of blood-brain-barrier penetration is likewise a design property inferred from central effects after peripheral dosing, and its most-cited in vivo demonstration sits in the retracted paper ^{2Reference 2Benoist CC et al. · 2014In vitroThe procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-Met system — animal (rat) / in vitro. [RETRACTED 2025 — retraction notice PMID 40312093]View study →}. There is no published human pharmacokinetic study of dihexa at all — no bioavailability figure, no half-life, no volume of distribution, no metabolite profile, no brain-exposure measurement. Community transdermal and DMSO-vehicle routes are entirely unvalidated. Reported in-vitro potency in the picomolar range comes from the compromised literature and should not be treated as an established constant.

Clinical & regulatory status

Dihexa has never been approved by any regulator, anywhere, for any indication, and it is not a lawful dietary-supplement ingredient. A ClinicalTrials.gov v2 API query for both “dihexa” and “PNB-0408” returns zero studies — the compound has never entered a registered human trial. There is no FDA, EMA, or TGA activity, no orphan or fast-track designation, and no IND that has produced a public record.

The broader HGF/MET-for-dementia thesis has been tested in humans, but through a structurally distinct successor molecule, fosgonimeton (ATH-1017), developed by Athira Pharma out of the same WSU research program. Fosgonimeton is not dihexa, and none of its regulatory history transfers. Verified against the registry: the Phase 2/3 LIFT-AD trial (NCT04488419) is listed as COMPLETED with 554 participants enrolled; its published primary analysis (N=287, subcutaneous fosgonimeton 40 mg vs placebo in participants not on acetylcholinesterase inhibitors) missed its primary endpoint — the Global Statistical Test combining ADAS-Cog11 and ADCS-ADL23 — and every secondary endpoint, with a between-group GST difference of −0.08 (p = 0.70) ^{16Reference 16Porsteinsson AP et al. · 2025RCTFosgonimeton in mild-to-moderate Alzheimer’s disease (LIFT-AD) — human (Phase 2/3 RCT), missed primary and all secondary endpoints; fosgonimeton, not dihexaView study →}. The Parkinson’s-dementia/DLB trial (NCT04831281, Phase 2, 28 enrolled) was terminated, the registry citing early enrollment closure “due to study design limitations”; the open-label extension (NCT04886063, 423 enrolled) was terminated explicitly because LIFT-AD did not meet the GST primary endpoint. Phase 1 was completed and well tolerated ^{14Reference 14Hua X et al. · 2022RCTSafety, tolerability, pharmacokinetics and pharmacodynamics of the positive modulator of HGF/MET, fosgonimeton, in healthy volunteers and subjects with Alzheimer’s disease — human (Phase 1 RCT), fosgonimeton, not dihexaView study →}.

Separately, three papers from the dihexa program were retracted in 2025 ^{2,11,12Reference 2Benoist CC et al. · 2014In vitroThe procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-Met system — animal (rat) / in vitro. [RETRACTED 2025 — retraction notice PMID 40312093]View study →Reference 11Kawas LH et al. · 2012In vitroDevelopment of angiotensin IV analogs as hepatocyte growth factor/Met modifiers — in vitro. [RETRACTED 2025 — retraction notice PMID 40312092]View study →Reference 12Kawas LH et al. · 2011In vitroMimics of the dimerization domain of hepatocyte growth factor exhibit anti-Met and anticancer activity — in vitro. [RETRACTED 2025 — retraction notice PMID 40312094]View study →} and the 2013 origin paper carries a 2021 Expression of Concern ^{1,17Reference 1McCoy AT et al. · 2013AnimalEvaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — animal (rat). [Expression of Concern, 2021 — see ref 17]View study →Reference 17American Society for Pharmacology et al. · 2021Notice of Concern: McCoy AT, et al. (2013), Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — expression of concernView study →}, following the institutional misconduct findings described above.

Fosgonimeton — a related but distinct molecule from the same program — has 1 completed Phase 1, 1 completed-and-negative Phase 2/3, and 2 terminated trials. Listed for mechanism context, not as dihexa evidence.

Last checked: July 2026.

Sourcing, Route & Legal Status

Regulatory status. Dihexa is an unapproved research chemical with no approved product anywhere in the world. It has never held a marketing authorization from the FDA, EMA, TGA, or any other regulator, has never been through a registered human trial, and is not a permitted dietary-supplement ingredient in the US, UK, EU, or Australia. It is not a scheduled or controlled substance in the US — but “not scheduled” is not “approved,” and marketing it for human consumption is unlawful in most Western jurisdictions. The regulatory posture here is simpler and starker than for most compounds here: there is no legitimate supply route for human use, because no legitimate human product exists.

How it’s supplied & administered. Every unit in circulation comes from research-chemical vendors, sold as powder or in solution and labeled “for research use only / not for human consumption” — while being marketed, in parallel, to biohackers as a cognitive enhancer. That contradiction is the whole business model, and it is worth naming: the “research use only” label is a liability shield, not a description of how the product is actually used. Because dihexa was designed for oral activity, community use is oral or transdermal (often in DMSO or oil vehicles) rather than injected, which removes the sterility risk that dominates injectable peptides but removes none of the identity risk. No route has been validated by any human pharmacokinetic study.

Sourcing reality (this is a safety issue, not a footnote). With no approved manufacturer, there is no pharmacopeial identity or purity standard for dihexa and no manufacturing oversight of any kind. Purity, correct structure, residual synthesis solvents, and contamination cannot be assumed and cannot be assessed by the buyer. A third-party certificate of analysis with HPLC identity and purity is the minimum a buyer might look for, but a COA from an uncredentialed laboratory is itself unverifiable, and the research-peptide market has a documented history of mislabeled and under-dosed product. This page does not recommend, rank, or link any vendor.

Safety

There is no human safety data for dihexa of any kind, and no formal toxicology program either — so read this as “un-assessed,” not “no evidence of harm.” Its designed mechanism amplifies HGF/c-Met, a pathway that approved cancer drugs exist to block.

Safety at a Glance

❔ Toxicity unknown

• No human safety data of any kind. No trial, no case series, no pharmacovigilance, no human pharmacokinetics to anchor an exposure estimate.
• It deliberately amplifies a known oncogenic pathway. c-Met inhibitors are approved cancer drugs; no carcinogenicity study of dihexa has ever been done.
• Never assessed in pregnancy or breastfeeding. HGF/c-Met signaling is central to normal embryonic development — see the box below.
• Current or previous cancer. A specific mechanistic reason for concern here, not a generic one — as is a known cancer predisposition.
• Interactions not assessed. Mechanistic caution with MET-targeted oncology drugs, which dihexa would directly oppose.

Full Safety & Interactions Detail

Overall posture — read this as “un-assessed,” not “no evidence of harm.” There is no human safety data for dihexa of any kind: no trial, no case series, no pharmacovigilance, no post-market surveillance, because there is no market and no trial. Beyond that, there is no formal toxicology program — no published repeat-dose toxicity study, no genotoxicity or Ames testing, no carcinogenicity study, no reproductive-toxicity study, and no human pharmacokinetics to anchor an exposure estimate. The rodent work was designed to test efficacy, not safety, and animals in those studies were not followed for tumor incidence over a lifespan. Everything below is inference from mechanism and class, and is labeled as such.

The oncology concern is the point of this section. Dihexa’s entire designed purpose is to potentiate signaling through HGF/c-Met. That axis is one of the better-characterized oncogenic pathways in human biology: c-Met drives proliferation, motility, invasion and metastasis across many tumor types, and c-Met inhibitors are approved cancer drugs — capmatinib and tepotinib in MET-altered non-small-cell lung cancer, among others. The same Washington State program that built dihexa also built HGF/Met antagonists, explicitly as anticancer agents: norleual was characterized as an HGF/c-Met inhibitor ^{13Reference 13Yamamoto BJ et al. · 2010In vitroThe angiotensin IV analog norleual can act as a hepatocyte growth factor/c-Met inhibitor — in vitroView study →} and a sibling paper reported “anti-Met and anticancer activity” for HGF dimerization-domain mimics ^{12Reference 12Kawas LH et al. · 2011In vitroMimics of the dimerization domain of hepatocyte growth factor exhibit anti-Met and anticancer activity — in vitro. [RETRACTED 2025 — retraction notice PMID 40312094]View study →} (that paper is among the retracted set). A compound engineered to push the identical pathway in the opposite direction, taken chronically by healthy people, with no carcinogenicity study and no human data, carries a theoretical proliferative risk that has never been assessed. This is not a demonstrated harm — no tumor signal has been reported in the rodent studies, but none of those studies were designed or powered to detect one. The honest framing is that this is a known-oncogenic pathway being deliberately amplified with the safety question left entirely open, which is a worse position than “no evidence of harm” makes it sound. Compare tesamorelin, where a comparable mechanistic concern (IGF-1 elevation) is serious enough that active malignancy is a labeled contraindication on an approved drug with a full clinical program behind it.

Interactions. Not assessed. No controlled interaction study exists. Mechanistic caution is warranted with anything modulating growth-factor, angiogenic, or c-Met signaling — including MET-targeted oncology drugs, where a positive modulator would be directly antagonistic to the intended therapy. This is class reasoning, not data.

Who should avoid it. Anyone with a current or previous cancer, a known cancer predisposition syndrome, or an undiagnosed proliferative lesion has a specific mechanistic reason for concern, not a generic one. So does anyone on MET-pathway oncology treatment. Beyond that: with zero human data, no one can be told this compound is safe — the correct statement is that nobody knows.

Scope disclosure (honesty, not a claim):

• Human data? None. Zero registered or published human trials; no case reports; no pharmacokinetics.
• Formal toxicology? None located — no repeat-dose toxicity, genotoxicity, or carcinogenicity study.
• Interactions assessed? No. Only mechanism-level cautions (growth-factor and c-Met-pathway drugs), which are inferred.
• Pregnancy/lactation assessed? No — no human or animal reproductive data.
• Long-term safety established? No. Absence of adverse-event reports reflects the absence of human study, not evidence of safety — and the growth-signaling mechanism makes long-term risk a live, uncharacterized question rather than an idle one.

Never imply safety from silence. Where dihexa has not been studied — which is everywhere a human is involved — the correct statement is “not assessed,” not “safe.”

Pregnancy & Lactation

? Not established in pregnancy? Not established in lactation

Not assessed and not established. There are no human pregnancy or lactation data and no animal reproductive or developmental toxicology studies for dihexa. HGF/c-Met signaling is central to normal embryonic development — placental, hepatic, and neuronal — so a compound designed to amplify it is exactly the kind of agent for which developmental toxicology would be mandatory before any human exposure. None has been done. Treat as contraindicated by default in pregnancy, in breastfeeding, and when trying to conceive.

Dosage

There is no established human dose for dihexa, and none is recommended here. No human has ever received dihexa in a published or registered study, so there is no dose-finding data, no maximum tolerated dose, no schedule, and no bioavailability figure with which to convert an animal dose into a human one. Any number circulating in community protocols or vendor copy is invented, not derived.

For context only, and explicitly not as a conversion basis: rodent studies used oral dosing in rats ^{1Reference 1McCoy AT et al. · 2013AnimalEvaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — animal (rat). [Expression of Concern, 2021 — see ref 17]View study →} and mice ^{4Reference 4Sun X et al. · 2021AnimalAngIV-analog dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via the PI3K/AKT signaling pathway — animal (mouse), independent groupView study →}, and 2–4 mg/kg by local, systemic, or intramuscular routes in the rat nerve-repair study ^{5Reference 5Weiss JB et al. · 2021AnimalStem cell, granulocyte-colony stimulating factor and/or dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model — animal (rat)View study →}. Rodent milligram-per-kilogram figures do not transfer to humans without pharmacokinetic bridging data, which for dihexa does not exist in any species-to-human form. This entry is informational only and makes no dosing recommendation.

References

1. McCoy AT, Benoist CC, Wright JW, et al. (2013). Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — animal (rat). [Expression of Concern, 2021 — see ref 17]. J Pharmacol Exp Ther. https://pubmed.ncbi.nlm.nih.gov/23055539/
2. Benoist CC, Kawas LH, Zhu M, et al. (2014). The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-Met system — animal (rat) / in vitro. [RETRACTED 2025 — retraction notice PMID 40312093]. J Pharmacol Exp Ther. https://pubmed.ncbi.nlm.nih.gov/25187433/
3. Benoist CC, Wright JW, Zhu M, et al. (2011). Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs — animal (rat). J Pharmacol Exp Ther. https://pubmed.ncbi.nlm.nih.gov/21719467/
4. Sun X, Deng Y, Fu X, et al. (2021). AngIV-analog dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via the PI3K/AKT signaling pathway — animal (mouse), independent group. Brain Sci. https://pubmed.ncbi.nlm.nih.gov/34827486/
5. Weiss JB, Phillips CJ, Malin EW, et al. (2021). Stem cell, granulocyte-colony stimulating factor and/or dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model — animal (rat). Ann Med Surg (Lond). https://pubmed.ncbi.nlm.nih.gov/34703584/
6. Wells RG, Azzam AF, Hiller AL, Sardinia MF. (2024). Effects of an angiotensin IV analog on 3-nitropropionic acid-induced Huntington’s disease-like symptoms in rats — animal (rat), negative result, independent group. J Huntingtons Dis. https://pubmed.ncbi.nlm.nih.gov/38489193/
7. Uribe PM, Kawas LH, Harding JW, Coffin AB. (2015). Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure — animal (zebrafish). Front Cell Neurosci. https://pubmed.ncbi.nlm.nih.gov/25674052/
8. Ho JK, Nation DA. (2018). Cognitive benefits of angiotensin IV and angiotensin-(1-7): a systematic review of experimental studies — systematic review (preclinical). Neurosci Biobehav Rev. https://pubmed.ncbi.nlm.nih.gov/29733881/
9. Wright JW, Harding JW. (2015). The brain hepatocyte growth factor/c-Met receptor system: a new target for the treatment of Alzheimer’s disease — review. J Alzheimers Dis. https://pubmed.ncbi.nlm.nih.gov/25649658/
10. Wright JW, Kawas LH, Harding JW. (2015). The development of small molecule angiotensin IV analogs to treat Alzheimer’s and Parkinson’s diseases — review. Prog Neurobiol. https://pubmed.ncbi.nlm.nih.gov/25455861/
11. Kawas LH, McCoy AT, Yamamoto BJ, et al. (2012). Development of angiotensin IV analogs as hepatocyte growth factor/Met modifiers — in vitro. [RETRACTED 2025 — retraction notice PMID 40312092]. J Pharmacol Exp Ther. https://pubmed.ncbi.nlm.nih.gov/22129598/
12. Kawas LH, Yamamoto BJ, Wright JW, Harding JW. (2011). Mimics of the dimerization domain of hepatocyte growth factor exhibit anti-Met and anticancer activity — in vitro. [RETRACTED 2025 — retraction notice PMID 40312094]. J Pharmacol Exp Ther. https://pubmed.ncbi.nlm.nih.gov/21859930/
13. Yamamoto BJ, Elias PD, Masino JA, et al. (2010). The angiotensin IV analog norleual can act as a hepatocyte growth factor/c-Met inhibitor — in vitro. J Pharmacol Exp Ther. https://pubmed.ncbi.nlm.nih.gov/20086056/
14. Hua X, Church K, Walker W, et al. (2022). Safety, tolerability, pharmacokinetics and pharmacodynamics of the positive modulator of HGF/MET, fosgonimeton, in healthy volunteers and subjects with Alzheimer’s disease — human (Phase 1 RCT), fosgonimeton, not dihexa. J Alzheimers Dis. https://pubmed.ncbi.nlm.nih.gov/35180125/
15. Johnston JL, Reda SM, Setti SE, et al. (2023). Fosgonimeton, a novel positive modulator of the HGF/MET system, promotes neurotrophic and procognitive effects in models of dementia — animal / in vitro, fosgonimeton, not dihexa. Neurotherapeutics. https://pubmed.ncbi.nlm.nih.gov/36538176/
16. Porsteinsson AP, Sabbagh M, Tariot PN, et al. (2025). Fosgonimeton in mild-to-moderate Alzheimer’s disease (LIFT-AD) — human (Phase 2/3 RCT), missed primary and all secondary endpoints; fosgonimeton, not dihexa. J Alzheimers Dis Rep. https://pubmed.ncbi.nlm.nih.gov/41393340/
17. American Society for Pharmacology and Experimental Therapeutics. (2021). Notice of Concern: McCoy AT, et al. (2013), Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — expression of concern. J Pharmacol Exp Ther. https://pubmed.ncbi.nlm.nih.gov/34551989/

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