Dihexa
Also known as: PNB-0408, N-hexanoic-Tyr-Ile-(6)-amino hexanoic amide
Dihexa (also called PNB-0408 or N-hexanoic-Tyr-Ile-(6)-amino hexanoic amide) is an angiotensin IV analog in the Hepatocyte growth factor modulator class. Dihexa is a small orally active molecule derived from angiotensin IV, developed as a modulator of hepatocyte growth factor signalling.
For research use only.
Key Facts
- CAS
- 1401708-83-5
- Molecular Weight (MW)
- 504.70 g/mol
- Half-life
- Not measured in humans; a terminal half-life of 12.68 days was reported in three rats after intravenous dosing
- FDA status
- Not Approved
- Evidence level
- Limited Human Evidence
- Human dose established
- No
- Administration Route
- Not established in humans
- Frequency
- Not established in humans
- Last updated
- Oct 5, 2026
- Reviewed
- Aug 30, 2026
- Targets
- HGF / c-Met
Vendor price snapshot
Each vendor counts once, at the median price per mg of its own listings; the typical range is the middle half of vendors. From public vendor listings collected between Dec 2025 and Oct 2026, so confirm the live price on the vendor site. Peptide Library does not sell peptides.
- Vendors listing this peptide
- 20
- Listed offers
- 35
- Median price per mg
- $5.50/mg
- Typical $0.376–$12.49/mg
Research summary
Orally active angiotensin IV analog that potentiates HGF/c-Met signaling in animal memory models. Not FDA-approved; human safety is not established.
Peptide Library's Dihexa profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.
Dihexa dosage: no established human dose
Dihexa has no established human dosage. No study has given dihexa itself to people, no trial of it is registered, and no human study of it is indexed. Its dosing literature is rodent work, led by a 2013 rat study that used 0.5 mg/kg per day by intraperitoneal injection and 2 mg/kg per day by mouth, and that now carries an expression of concern from the journal. The only human exposure on record is indirect: fosgonimeton, an injectable prodrug that the body converts into dihexa, was tested in healthy volunteers and in people with Alzheimer's disease, and did not meet its primary or secondary endpoints in a phase 2/3 trial.
No established human dosage.
Human clinical evidence: None identified.
Preclinical research: Dihexa (PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) was developed at Washington State University from Nle1-angiotensin IV, with the aim of a procognitive compound stable enough in blood to reach the brain. The founding 2013 rat study reported reversal of a scopolamine-induced spatial learning deficit after oral, intraperitoneal or direct brain dosing, better learning in a small group of aged rats, and more dendritic spines and synapses in cultured hippocampal neurons; in three rats it measured a terminal half-life of 12.68 days after intravenous dosing. A 2014 paper attributing those effects to potentiation of hepatocyte growth factor and its receptor MET has since been retracted. Work from other groups is limited and mixed: benefit in Alzheimer-model mice and in a rat brain-injury model dosed directly into the brain, and no protection in a rat model of Huntington's disease. Athira Pharma later developed fosgonimeton, an injectable phosphate prodrug of the same molecule, and took it into human trials, where it did not meet its efficacy endpoints. No study has given dihexa itself to people, and animal dosing is not converted into a human equivalent anywhere on this page.
Animal dosing is not converted into a human dose anywhere on this page. Where research figures appear below, they are reported as studied, not recommended.
| Human dosing established | No |
|---|---|
| Route | Not established in humans |
| Half-life | Not measured in humans; a terminal half-life of 12.68 days was reported in three rats after intravenous dosing |
| Evidence level | Limited Human Evidence |
| Last reviewed | 2026-10-05 |
Preclinical and analog research
Not human dosing evidence. Listed for completeness and never extrapolated to a human dose.
| Study / context | Population | Dose | Route | Frequency | Duration | Outcome studied | Source |
|---|---|---|---|---|---|---|---|
| Preclinical — scopolamine-induced learning deficit in rats, three routesPreclinical · Preclinical rodent study from the originating laboratory; the journal published an expression of concern about this paper in 2021 | Three-month-old male Sprague-Dawley rats given scopolamine directly into the brain, 8-10 per group | 0.05, 0.25 or 0.50 mg/kg intraperitoneally; 1.25 or 2.0 mg/kg by oral gavage; 0.1 or 1 nmol directly into the brain. The highest dose by each route reversed the deficit; 0.05 mg/kg intraperitoneally did not | Intraperitoneal, oral (gavage) and intracerebroventricular, in separate experiments | Daily, shortly before each day's water maze training | 8 days of training, with a probe trial on day 9 | Morris water maze escape latency and probe-trial performance; at the highest dose by each route, treated rats were indistinguishable from controls not given scopolamine | Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013. |
| Preclinical — aged ratsPreclinical · Preclinical rodent study from the originating laboratory; the journal published an expression of concern about this paper in 2021 | 24-month-old Sprague-Dawley rats, 3 male and 3 female per group, not prescreened for cognitive impairment | 2 mg/kg | Oral, by gavage, as a suspension in isotonic saline | Once daily before testing | 8 days of water maze testing | Learning curve better than in untreated aged rats (Mann-Whitney P < 0.03) | Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013. |
| Preclinical — fosgo-AM (ATH-1001), the compound the FDA substance registry lists as dihexa, in the rat scopolamine modelPreclinical · Preclinical rodent study by Athira Pharma, which names the compound fosgo-AM rather than dihexa | 14-week-old male Sprague Dawley rats given scopolamine directly into the brain | 1 mg/kg in DMSO | Subcutaneous | Once daily, 45 minutes before testing | 8 days of water maze training, with a probe trial on day 9 | Reversed the scopolamine-induced water maze deficit. The same paper reports poor stability in simulated gastric and intestinal fluid, poor and variable oral bioavailability, and aqueous solubility below 50 micrograms per mL | Fosgonimeton, a Novel Positive Modulator of the HGF/MET System, Promotes Neurotrophic and Procognitive Effects in Models of Dementia. Neurotherapeutics. 2023. |
| Preclinical — APP/PS1 Alzheimer-model micePreclinical · Preclinical rodent study from an independent group | Six-month-old male APP/PS1 mice | 1.44 or 2.88 mg/kg | The methods describe the route as intragastric in one sentence and intraperitoneal in the next; the results describe it as intragastric | — | Three months, from six to nine months of age | Improved Morris water maze performance, less astrocyte and microglial activation, lower IL-1 beta and TNF-alpha and higher IL-10, attributed to PI3K/AKT signalling | AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway. Brain Sci. 2021. |
| Preclinical — working memory after repeated mild traumatic brain injuryPreclinical · Preclinical rodent study from an independent group | Long-Evans rats, 33 male and 19 female, after repeated closed-head mild brain injury | 1.0 pmol or 1.0 nmol per day directly into the brain; the authors describe a dose-dependent effect, with the improvement shown at 1 nmol per day | Intracerebroventricular infusion | Once daily, 5 minutes before testing | 5 days | T-maze working memory better than in vehicle-treated injured rats at 1 nmol per day; the effect was blocked by the MET antagonist Hinge | Hepatocyte Growth Factor/MET Activator Rescues Working Memory Deficits after Repeated Mild Traumatic Brain Injury. Neurotrauma Rep. 2025. |
| Preclinical — 3-nitropropionic acid model of Huntington's diseasePreclinical · Preclinical rodent study from an independent group, with a negative result | 40 male Wistar rats in three groups | Not stated in the abstract; given alongside chronic 3-nitropropionic acid exposure | Not stated in the abstract | — | Five weeks | Did not protect against the weight, motor or cognitive deficits produced by 3-nitropropionic acid | Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats. J Huntingtons Dis. 2024. |
| Phase 1 trial of fosgonimeton (NCT03298672), a phosphate prodrug of dihexa, not dihexa itselfClinical trial · Phase 1 trial of a prodrug that the body converts to dihexa, not dihexa itselfStudied an analog, not Dihexa itself | 88 participants: healthy young men, healthy elderly adults and people with Alzheimer's disease | Fosgonimeton, not dihexa: single doses of 2, 6, 20, 40, 60 or 90 mg in healthy young men; 20, 40, 60 or 80 mg daily in healthy elderly adults; 40 mg daily in people with Alzheimer's disease | Subcutaneous | Once daily | Single dose, or 9 days | Reported as safe and well tolerated at every dose, with dose-proportional pharmacokinetics; EEG and P300 latency were the pharmacodynamic measures | Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Positive Modulator of HGF/MET, Fosgonimeton, in Healthy Volunteers and Subjects with Alzheimer's Disease: Randomized, Placebo-Controlled, Double-Blind, Phase I Clinical Trial. J Alzheimers Dis. 2022. |
| LIFT-AD (NCT04488419) — phase 2/3 trial of fosgonimeton, a phosphate prodrug of dihexa, not dihexa itselfClinical trial · Phase 2/3 randomised controlled trial of a prodrug that the body converts to dihexa, not dihexa itselfStudied an analog, not Dihexa itself | People with mild-to-moderate Alzheimer's disease; primary analysis of 287 participants not taking acetylcholinesterase inhibitors | Fosgonimeton 40 mg daily, not dihexa; participants randomised to 70 mg were included in the safety analysis | Subcutaneous | Once daily | 26 weeks | Did not achieve its primary endpoint, a combined cognition and daily-function score, or its secondary endpoints. Serious adverse events occurred in 4.2% on fosgonimeton and 6.9% on placebo; 14.2% stopped because of adverse events versus 4.6% on placebo, mostly injection-site reactions | Fosgonimeton in mild-to-moderate Alzheimer's disease. J Alzheimers Dis Rep. 2025. |
Where sources disagree
- Dihexa circulates with oral, topical and injected protocols measured in milligrams per day. No human study has given dihexa itself at any dose, by any route, and no primary source for those figures could be identified.
- The claim that dihexa is ten million times, or seven orders of magnitude, more potent than BDNF comes from Washington State University's October 2012 press release, which described bench assays counting new connections between cultured nerve cells. The peer-reviewed paper released with it reports more dendritic spines on cultured rat hippocampal neurons at a dihexa concentration of 10^-12 M, but contains no comparison with BDNF, and no published dataset behind the figure could be identified. Either way it is a cell-culture comparison, not a measure of effect in an animal or a person, and potency in a dish says nothing about a dose.
- Fosgonimeton (ATH-1017) is a phosphate prodrug of dihexa. The FDA's Global Substance Registration System lists dihexa as its active metabolite and ATH-1001 as one of dihexa's names, and Athira Pharma's 2023 paper calls the active metabolite fosgo-AM, previously ATH-1001, without using the name dihexa. Its Alzheimer's trials gave 40 or 70 mg of the prodrug by daily subcutaneous injection, and the phase 2/3 LIFT-AD trial did not meet its primary or secondary endpoints. That is the closest thing to human dosing evidence for dihexa, and it is not a dihexa dose: it is a dose of a different compound, injected rather than swallowed, that did not demonstrate benefit. This page does not convert it into a dihexa equivalent.
- The case for taking dihexa by mouth rests on the 2013 rat study, which describes it as orally active. Athira's data on the same molecule point the other way: its active metabolite was largely broken down in simulated gastric and intestinal fluid, with 7.8% and 0.1% remaining after an hour, had poor and highly variable oral bioavailability, and was judged likely unsuitable as an oral drug. Athira also reported its aqueous solubility as below 50 micrograms per mL, the reason it developed an injectable prodrug. The rodent studies reviewed here gave dihexa in DMSO-based vehicles or as a suspension, and this page gives no reconstitution figures for it.
- The literature rests heavily on one laboratory and has integrity problems. In 2025 the Journal of Pharmacology and Experimental Therapeutics retracted the 2014 paper that proposed dihexa's HGF/MET mechanism, after a Washington State University investigation found falsified and/or fabricated data in it; two earlier papers from the same laboratory on compounds targeting the HGF/MET system were retracted at the same time. The 2013 paper that introduced dihexa and reported its rodent dosing has carried an expression of concern from the same journal since 2021. Independent work is limited to a few rodent studies with mixed results.
- Hepatocyte growth factor and its receptor MET mediate cell proliferation, migration and tissue formation, and dysregulation of the system is linked to tumour formation, metastasis and tumour blood-vessel growth. A 2015 Washington State University patent application on dihexa says so, notes that c-Met is recognised as an oncogene, and states that short-duration safety studies found no neoplastic induction; those studies are not published. No long-term safety or toxicology study of dihexa is indexed. The only controlled human safety data involving dihexa come from fosgonimeton trials, in which the prodrug was injected and the placebo-controlled period lasted 26 weeks.
- Dihexa is not a natural peptide. It is a synthetic derivative of angiotensin IV in which two amino acids, tyrosine and isoleucine, are capped with a hexanoyl group at one end and a 6-aminohexanoic amide at the other, to resist breakdown and cross the blood-brain barrier. Its developers and Athira describe this class of compounds as small molecules.
Handling & administration
- Injection Sites
- Abdomen
- Timing Notes
- Investigational; formulations vary (oral/topical reported).
Sequence & molecular data
| Amino acid sequence | Hexanoyl-Tyr-Ile-Ahx-NH2 |
|---|---|
| Molecular formula | C27H44N4O5 |
| Molecular weight | 504.70 g/mol |
| CAS number | 1401708-83-5 |
| Half-life | Oral; long CNS residence reported in animals |
| Appearance | White lyophilized powder |
| Formulation | Lyophilized Powder |
| PubChem CID | 129010512 |
| FDA UNII | 9WYX65A5C2 |
Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.
Science
Mechanism of Action
Dihexa is a small orally active molecule derived from angiotensin IV, developed as a modulator of hepatocyte growth factor signalling. It binds HGF and enhances its activation of the c-Met receptor tyrosine kinase, potentiating signalling rather than acting as a direct receptor agonist. In hippocampal preparations this promotes dendritic spine formation and synaptogenesis, and rodent studies report cognitive effects at very low doses. Two caveats matter for interpretation: potency in rodent models does not establish clinical cognitive benefit, and c-Met is a proto-oncogene, so sustained potentiation of that pathway carries a theoretical proliferative concern that has not been characterised in humans.
Origin
Synthetic N-hexanoic-Tyr-Ile aminohexanoic amide.
Targets
Studies
- Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies
- 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
- AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
- Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions
- The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases
Regulatory & research status
Dihexa is not an FDA-approved product. It is sold for laboratory research and has no approved medical use.
| FDA status | Not Approved |
|---|---|
| Availability | Research-Only |
| WADA (sport) | Unknown / Not Listed |
| Library classification | Research-Only |
Benefits
Dihexa side effects
Dihexa has only limited human data, so the list below is incomplete and its side-effect profile is not well established.
Side Effects
- Unknown human AE profile
- Theoretical growth-factor risks
Storage & stability
Lyophilized (freeze-dried) peptide powder is far more stable than the reconstituted solution. Keep sealed vials cold, dry and away from light; long-term storage is typically frozen, with short-term refrigeration for vials in use.
Once reconstituted in bacteriostatic water, keep the solution refrigerated, avoid repeated freeze–thaw cycles and agitation, and label the vial with the reconstitution date and concentration. Discard any solution that turns cloudy or shows particulates.
Degradation rates differ by sequence: peptides containing methionine, cysteine, asparagine or glutamine are more prone to oxidation and deamidation, so shelf life after reconstitution is compound-specific rather than universal.
Read the full guide: how to store peptides before and after reconstitution →
Source: Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm Res. 2010;27(4):544–575. (PMID 20143256). General guidance for research handling; not product-specific instructions.
Dihexa: frequently asked questions
What is Dihexa?
Orally active angiotensin IV analog that potentiates HGF/c-Met signaling in animal memory models. Not FDA-approved; human safety is not established.
How does Dihexa work?
Dihexa is a small orally active molecule derived from angiotensin IV, developed as a modulator of hepatocyte growth factor signalling. It binds HGF and enhances its activation of the c-Met receptor tyrosine kinase, potentiating signalling rather than acting as a direct receptor agonist.
Is Dihexa FDA approved?
No. Dihexa is not approved by the FDA for any indication and is categorised as research-only. It has not been reviewed for safety or efficacy as a medicine, and published research should be read as investigation rather than established use.
What is the half-life of Dihexa?
Reported half-life for Dihexa is Oral; long CNS residence reported in animals. Half-life describes how long the compound persists in circulation, not how long any effect lasts, and published figures vary with route of administration, formulation and the population studied.
What is the amino acid sequence of Dihexa?
Dihexa has the sequence Hexanoyl-Tyr-Ile-Ahx-NH2, giving a chain of 5 amino acids. Its molecular formula is C27H44N4O5.
What peptides are similar to Dihexa?
Compounds most often compared with Dihexa include Cerebrolysin, Cortexin, P21 (BDNF-mimetic peptide) and Noopept. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.
References
- Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies — Neurosci Biobehav Rev, 2018External reference
- 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), 2021External reference
- AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway — Brain Sci, 2021External reference
- Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions — J Am Acad Orthop Surg Glob Res Rev, 2026External reference
- The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases — Prog Neurobiol, 2015External reference
Related research, comparisons & guides
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Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Oct 5, 2026 · Version 3
This Dihexa profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error
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