Dihexa

An orally active, blood brain barrier permeant compound derived from angiotensin IV, studied in animals as an activator of the HGF/c-Met system. No human trial of dihexa itself is registered, the published animal abstracts do not state the doses used, and the human injection trials often linked to it tested a different molecule, fosgonimeton.

Last updated: September 2026

What is Dihexa?

Dihexa is the compound N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (PubChem CID 129010512, molecular formula C27H44N4O5, molecular weight 504.7, CAS 1401708-83-5). It was built from the first three amino acids of Nle1-angiotensin IV, so its backbone carries a tyrosine and an isoleucine residue capped at both ends with chemical groups, and it is also cataloged under the developmental codes PNB-0408 and ATH-1001. It sits in our peptide library alongside the other research compounds.

Whether dihexa is even "a peptide" is contested in the literature, and this page presents that as a real disagreement rather than picking a side. The groups that developed it call it "a small molecule" (PMID 25455861, 25649658); a 2026 review lists it among "neuroactive peptides" next to selank and semax (PMID 41490200); a vendor page calls it "a small peptide." What is not in dispute: it is a 504.7 Da molecule containing two standard amino acid residues joined by an amide bond, derived from angiotensin IV. We use "compound" and let the sources speak.

Mechanistically, dihexa binds hepatocyte growth factor (HGF) with high affinity and triggers c-Met receptor activation even when HGF is scarce, and it promotes new hippocampal synapse formation in animal and cell studies (PMID 25187433). A separate study describes it as a synthetic HGF mimetic that dimerizes with endogenous HGF to form a functional ligand (PMID 25674052). It is reported to be orally active and to cross the blood brain barrier (PMID 23055539, 25649658). Every one of those findings comes from animal or cell studies.

One caution up front, because it drives most of the confusion online: the human injection trials often attributed to dihexa did not use dihexa. They used fosgonimeton (ATH-1017), a separate molecule that adds a phosphate group to the same skeleton (PubChem CID 156596375, formula C27H45N4O8P), given by daily subcutaneous injection. Wikipedia describes fosgonimeton as a phosphate prodrug of dihexa, though that word appears in no primary source retrieved for this page. Read the two as related but distinct.

How It Works

HGF/c-Met activation: dihexa binds hepatocyte growth factor with high affinity and induces c-Met phosphorylation in the presence of subthreshold HGF, behaving as a synthetic HGF mimetic that dimerizes with endogenous HGF to form a functional ligand (animal and in vitro, PMID 25187433, 25674052).

Synaptogenesis: in the same work, dihexa drives hippocampal spinogenesis and synaptogenesis comparable to HGF itself, and blocking HGF or knocking down c-Met abolishes the effect, tying the cognitive readouts to this pathway (animal, PMID 25187433).

Downstream signaling: in APP/PS1 Alzheimer's-model mice, orally administered dihexa activated the PI3K/AKT pathway, and the PI3K inhibitor wortmannin reversed its anti-inflammatory and anti-apoptotic effects; in zebrafish, the protective effect was attenuated by Akt, TOR, and MEK inhibitors (animal, PMID 34827486, 25674052).

Origin and target debate: dihexa is an angiotensin IV analog, and the field still disputes the identity of the AT4 receptor, with evidence offered both for insulin-regulated aminopeptidase (IRAP) and, from the dihexa group, for the brain HGF/c-Met system (review, PMID 25455861, 25649658).

What the Research Reports

Procognitive activity in rat models: dihexa showed excellent antidementia activity in the scopolamine and aged rat models, with marked synaptogenic activity (animal study, rat, PMID 23055539).
Memory rescue in an Alzheimer's mouse model: in APP/PS1 mice, oral dihexa restored spatial learning in the Morris water maze, increased neuronal counts and synaptophysin, and lowered the pro-inflammatory cytokines IL-1 beta and TNF-alpha while raising anti-inflammatory IL-10 (animal study, mouse, oral, PMID 34827486).
Synaptogenesis via HGF/c-Met: dihexa induced hippocampal spinogenesis and synaptogenesis dependent on the HGF/c-Met system (animal and in vitro, PMID 25187433).
Hair-cell protection in zebrafish: a bath concentration of 1 micromolar gave optimal protection against two ototoxic antibiotics in the larval zebrafish lateral line, which is a concentration in water and not a body-weight dose (animal study, larval zebrafish, immersion, PMID 25674052).
A clearly negative result: in a rat Huntington's model, PNB-0408 (dihexa) did not protect Wistar rats from 3-nitropropionic acid neurotoxicity across five weeks, and the authors concluded it may not be an efficacious strategy in that model (animal study, rat, PMID 38489193).
Class-level review: a systematic review of 32 non-human studies of brain renin-angiotensin-system peptides (angiotensin IV and angiotensin-(1-7)) including dihexa found that eight of nine cognitive-deficit studies of angiotensin IV and its analogs reported improved spatial working memory or passive avoidance, and that the class appeared most effective when given intracerebroventricularly (systematic review of non-human studies, PMID 29733881).
Laboratory reagent: outside the cognition work, dihexa is used as a hepatocyte growth factor agonist to help differentiate stem cells into liver-like cells (in vitro, PMID 27532814).

Doses Described in the Research

Phase	Dose	Frequency	Duration
Original characterization (rat)	Dose not stated in the abstract (animal study, rat, described only as "orally active", PMID 23055539)	Not stated in the abstract	Not stated in the abstract
HGF/c-Met dependence	Dose not stated in the abstract (animal study, species not named, oral, PMID 25187433)	Oral dihexa; HGF antagonist given intracerebroventricularly	Not stated in the abstract
Alzheimer's model (APP/PS1 mouse)	Abstract states only 'different doses', no figure (animal study, mouse, oral, PMID 34827486)	Oral administration	Not stated in the abstract
Huntington's model (Wistar rat), negative result	Dose not stated in the abstract (animal study, rat, route not stated, PMID 38489193)	Route not stated in the abstract	Measured over five weeks; n=40 across three groups
Zebrafish ototoxicity (larva)	1 micromolar bath concentration, not a body-weight dose (animal study, larval zebrafish, immersion, PMID 25674052)	Immersion (concentration in water)	Acute exposure
Fosgonimeton, LIFT-AD trial (different molecule)	40 mg, with a separate 70 mg group; fosgonimeton not dihexa (trial dose, not a recommendation, ClinicalTrials.gov NCT04488419)	Daily subcutaneous injection	26 weeks; n=554
Fosgonimeton, ACT-AD trial (different molecule)	40 mg and 70 mg; fosgonimeton not dihexa (trial dose, not a recommendation, ClinicalTrials.gov NCT04491006)	Daily subcutaneous injection	26 weeks; n=77

No dihexa study collected for this page states a milligram dose; the animal abstracts record only that a dose was given, and one says merely 'different doses'. The 40 mg and 70 mg figures belong to fosgonimeton (ATH-1017), a different, phosphate-bearing molecule given by daily subcutaneous injection, not to dihexa and not by mouth. These rows are educational, not a recommendation or a protocol. Any dose or decision to use a compound belongs with a licensed prescriber.

Side Effects

Dihexa itself

⚠No side-effect, toxicity, or tolerability data for dihexa appears in any study collected for this page. Every dihexa abstract reported efficacy, mechanism, or outcome findings only (PMID 23055539, 25187433, 34827486).
⚠There is no maximum tolerated dose and no human safety study of dihexa. Absence of reported harms is not evidence of safety.
⚠The one safety-adjacent animal observation is a lack of benefit, not a harm: in a Huntington's model, PNB-0408 did not protect Wistar rats and no harm attributable to it was reported (PMID 38489193).

Fosgonimeton (a different molecule)

•Human adverse events exist only for fosgonimeton (ATH-1017), a different molecule given by a different route from dihexa: the trials tested 40 mg and 70 mg once daily by subcutaneous injection for 26 weeks (trial doses, not a recommendation, ClinicalTrials.gov NCT04488419 and NCT04491006).
•In that trial the clearest dose-linked signals were injection-site reactions (128 of 224 at 40 mg versus 31 of 218 on placebo) and eosinophilia (16 of 224 versus 0 of 218) (fosgonimeton, NCT04488419).
•Injection-site reactions are an artifact of subcutaneous injection and say nothing about an orally studied compound; deaths were zero in all groups, and the record posted no statistical analysis (fosgonimeton, NCT04488419).

Who Should NOT Use Dihexa

✕This is educational content, not medical guidance, and not a contraindication list. Dihexa has no registered human trial of its own: a ClinicalTrials.gov search for 'dihexa' returns zero studies.
✕Because no human safety, toxicity, or tolerability data for dihexa was found in any source used here, no one can responsibly state who may use it safely. Absence of reported harms is not evidence of safety.
✕Pregnancy, breastfeeding, existing illness, or other medications: there is no dihexa data to weigh any of these. Any decision belongs with a licensed physician, not a website.

Where the Evidence Stands

Human trials

None for dihexa. A ClinicalTrials.gov search for 'dihexa' returns zero studies, and a 2026 review of the class it belongs to states there is a current lack of clinical trials (PMID 41490200).

Animal data

Cognitive improvement in scopolamine, aged-rat, and APP/PS1 mouse models (PMID 23055539, 34827486), one clearly negative result in a rat Huntington's model (PMID 38489193), and hair-cell protection in zebrafish (PMID 25674052). None of these abstracts states the dose used.

Mechanism

Consistent evidence that dihexa activates the HGF/c-Met system and promotes hippocampal synapse formation in animal and cell studies (PMID 25187433). Whether that carries over to people is untested.

Often confused

The human injection trials people attribute to dihexa tested fosgonimeton (ATH-1017), a different, phosphate-bearing molecule given subcutaneously (NCT04488419). Those results are not dihexa results.

Notes from Ho Chi Minh City

The easiest way to go wrong with dihexa is to read the ATH-1017 injection-trial results as if they were dihexa results. They are not. Those trials used fosgonimeton (ATH-1017), a phosphate-bearing molecule given by daily subcutaneous injection, while dihexa itself is an oral research compound with zero registered human trials of its own: a ClinicalTrials.gov search for dihexa returns nothing. The confusion even shows up in the reference material, where Wikipedia calls fosgonimeton a phosphate prodrug of dihexa, wording that appears in no primary source retrieved for this page. Neither Long Châu nor Pharmacity returns a dihexa product on its own search page, and the national DAV registration database would not load from here, so no one can honestly call it registered or banned in Vietnam either way. Dose, route, and any decision to use a research compound sit with a licensed prescriber, not a forum thread.

Sourcing in Vietnam

Dihexa is not stocked by the Vietnamese pharmacy chains that publish searchable catalogs. A search for dihexa on Long Châu returns products for dexa instead, its own spell-correction, and Pharmacity returns the string Không tìm thấy sản phẩm, meaning no products found. That is a retail-listing fact, not a registration fact. The DAV portal, drugbank.vn, and An Khang could not be reached for this page, so Vietnamese registration status is not established either way, and no price exists to quote because no chain returns the product. Where dihexa is sold, it is sold as a research chemical: one vendor page that did load, Creative Peptides, lists the compound and its CAS number but shows no price, no certificate of analysis, and no purity figure. Treat any dihexa listing without a batch certificate of analysis as unverified.

FAQ

Q: Is dihexa a peptide or a small molecule?

A: The sources disagree. The groups that developed it call it "a small molecule" (PMID 25455861, 25649658); a 2026 review lists it among "neuroactive peptides" with selank and semax (PMID 41490200); a vendor calls it "a small peptide." Structurally it is a 504.7 Da molecule with two amino acid residues (tyrosine and isoleucine) derived from angiotensin IV, so it sits on the boundary. We call it a compound and cite the disagreement rather than pick a side.

Q: Are there human studies of dihexa?

A: No. A ClinicalTrials.gov query for "dihexa" returns zero studies, and a 2026 review of its class notes a current lack of clinical trials (PMID 41490200). The human trials often cited for dihexa actually studied fosgonimeton (ATH-1017), a different molecule given by subcutaneous injection.

Q: What dose of dihexa did the animal studies use?

A: The published abstracts do not say. Every in vivo dihexa abstract collected for this page reports that a dose was given without stating the milligram amount, and one says only "different doses" (PMID 34827486). This page reports that gap rather than filling it with a number from a vendor or a forum. No figure here is a recommendation.

Q: Is dihexa the same as fosgonimeton or ATH-1017?

A: No. Fosgonimeton (ATH-1017, PubChem CID 156596375, formula C27H45N4O8P) is the same carbon skeleton with a phosphate group added to the tyrosine, given by daily subcutaneous injection in Alzheimer's trials. Dihexa (CID 129010512, C27H44N4O5) is the oral research compound with no trial of its own. Wikipedia calls fosgonimeton a phosphate prodrug of dihexa, wording that appears in no primary source retrieved here.

Q: Is dihexa approved or sold in Vietnam?

A: No FDA drug label lists dihexa (the openFDA label database returns no match) and no human trial of it is registered, but this page cannot say it is unapproved everywhere. In Vietnam, Long Châu and Pharmacity return no dihexa product on their own search pages, while the DAV registration portal, drugbank.vn, and An Khang could not be reached for this page, so its registration status there is not established either way. No retail price exists to quote.

Q: Is dihexa really 'seven orders of magnitude more potent than BDNF'?

A: That figure comes only from Wikipedia, a tertiary source, and appears in none of the primary studies retrieved for this page. Treat it as an unverified secondhand claim, not an established measurement.

Where to Get Dihexa in Vietnam

This page is an evidence profile, not a storefront. Dihexa is not returned by the searchable catalogs of Long Châu or Pharmacity; where it is sold at all, it is sold as a research chemical, and no vendor page reviewed for this profile published a certificate of analysis or a purity figure. We describe what the studies report and do not endorse or link any seller. For related compounds and background, browse the research library.

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Research & Sources

Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents · J Pharmacol Exp Ther (2013) (PMID: 23055539)
Original characterization; scopolamine and aged-rat models. Dose not stated in the abstract.
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) (PMID: 25187433)
HGF/c-Met dependence of dihexa effects. Oral dihexa. Dose not stated in the abstract.
AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway · Brain Sci (2021) (PMID: 34827486)
APP/PS1 Alzheimer's mouse; oral. Abstract states only 'different doses', no figure.
Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats · J Huntingtons Dis (2024) (PMID: 38489193)
Negative result: PNB-0408 (dihexa) did not protect Wistar rats in a 3-NP model. Dose and route not stated in the abstract.
Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure · Front Cell Neurosci (2015) (PMID: 25674052)
Zebrafish lateral line; 1 micromolar bath concentration (not a body-weight dose).
Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies · Neurosci Biobehav Rev (2018) (PMID: 29733881)
Systematic review of non-human studies only.
The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases · Prog Neurobiol (2015) (PMID: 25455861)
Review; calls dihexa a small molecule.
The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease · J Alzheimers Dis (2015) (PMID: 25649658)
Review; brain HGF/c-Met as an AD target.
Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions · J Am Acad Orthop Surg Glob Res Rev (2026) (PMID: 41490200)
2026 review; lists dihexa among neuroactive peptides and notes a current lack of clinical trials.
Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells · Curr Protoc Stem Cell Biol (2016) (PMID: 27532814)
In vitro use of dihexa as an HGF agonist reagent.
PubChem Compound: Dihexa (CID 129010512) · PubChem (2026) Link
Dihexa: C27H44N4O5, MW 504.7, CAS 1401708-83-5. Accessed 2026-09-06.
PubChem Compound: Fosgonimeton (CID 156596375) · PubChem (2026) Link
Fosgonimeton (ATH-1017): C27H45N4O8P, MW 584.6. A different molecule from dihexa. Accessed 2026-09-06.
ClinicalTrials.gov search: dihexa · ClinicalTrials.gov (2026) Link
Query for 'dihexa' returns zero registered studies. Accessed 2026-09-06.
LIFT-AD: ATH-1017 (fosgonimeton) in Mild to Moderate Alzheimer's Disease (NCT04488419) · ClinicalTrials.gov (2024) Link
Fosgonimeton, 40 mg daily subcutaneous, 26 weeks, n=554. Not dihexa. No statistical analysis posted.
ACT-AD: ATH-1017 (fosgonimeton) in Mild to Moderate Alzheimer's Disease (NCT04491006) · ClinicalTrials.gov (2022) Link
Fosgonimeton 40 mg and 70 mg daily subcutaneous, n=77. Not dihexa.
openFDA drug label API: dihexa · openFDA (2026) Link
Query for dihexa returns NOT_FOUND (a statement about FDA labels only, not worldwide approval).
Nhà thuốc Long Châu search: dihexa · Nhà thuốc Long Châu (2026) Link
Search for 'dihexa' returns no product; the site spell-corrects to 'dexa'. Retail listing, not registration. Accessed 2026-09-06.
Pharmacity search: dihexa · Pharmacity (2026) Link
Search for dihexa returns no products (no products found). Accessed 2026-09-06.
Creative Peptides: Dihexa product page · Creative Peptides (2026) Link
Vendor page; lists dihexa and CAS 1401708-83-5 with no price, COA, or purity figure. Not a clinical source.
Dihexa · Wikipedia (2026) Link
Tertiary. Source of the 'phosphate prodrug' wording and the 'seven orders of magnitude vs BDNF' claim, neither found in any primary source retrieved.

Important Disclaimer

Educational content only. Not medical advice. Dihexa has no registered human clinical trial of its own and no FDA drug label lists it; this page describes what animal and laboratory research reports, not a treatment. It is not listed in the searchable catalogs of Long Châu or Pharmacity, and its status with the Drug Administration of Vietnam (DAV) could not be determined for this page. Consult a licensed physician before any use.