Dihexa

Dihexa is a synthetic analogue of angiotensin IV, built at Washington State University by cutting the parent peptide down to its Tyr-Ile core.

Preclinical-heavyPeptide research profile

Also known as: PNB-0408, ATH-1001, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, Hexanoyl-Tyr-Ile-Ahx-NH2, UNII 9WYX65A5C2, DTXSID701032895

(how we review)

Dosing & scaling, explained

Amounts reported for Dihexa are listed under Reported protocols, each with its source and study kind. No amount ladder is inferred from them. This is educational source context, not a protocol or recommendation.

No source-supported amount ladder is shown

Enter a target amount only from your own reviewed source. The calculator can convert it into concentration, volume and device markings, but it will not infer an amount from product availability or another compound.

Only mcg or mg amounts are retained. The calculator derives mL, syringe units or pen clicks from the current vial strength, water volume and device.

No independently verified schedule

Clinical context

No human amount or schedule has been recorded for this compound.

Storage, handling and interpretation

Product identity

Verify the exact compound, formulation and amount against the product label or certificate before calculation.

Storage & handling

Follow the product label, certificate and validated laboratory SOP; no universal storage assumption is applied here.

Prepared solutions

Label concentration and preparation date, use sterile technique where applicable, and follow a validated stability protocol.

Reported protocols for Dihexa

What published studies and recent community write-ups report about amounts, timing and course length. 4 preclinical and 4 community-reported rows, each linked to its source. These are descriptions of what others report, not instructions, and nothing here is medical advice.

ContextDoseFrequencyRouteCourseSource
Preclinical4 rows
Original oral dose-finding in rat dementia modelsRats with scopolamine-induced memory deficits and aged rats, tested in the Morris water mazeOral doses in the scopolamine and aged-rat models; the indexed abstract states no figure, and secondary summaries give about 2 mg/kg per dayNot statedOralNot statedJournal of Pharmacology and Experimental Therapeutics (PubMed)2013
This is the paper that first described Dihexa, reporting that the modified tripeptide core stayed active by mouth, reversed scopolamine-induced water-maze deficits and increased hippocampal synaptogenesis. The record carries a 2021 expression of concern printed by the journal, so its specifics deserve extra caution, and every figure in it is a rat figure that does not convert to a human amount.
APP/PS1 Alzheimer-model miceAPP/PS1 transgenic mice dosed from six to nine months of age, with wild-type controls1.44 mg/kg or 2.88 mg/kgOnce dailyIntragastric3 monthsNone describedBrain Sciences (PubMed Central)2021
Both amounts shortened water-maze escape latency, raised neuronal counts and synaptophysin, lowered IL-1 beta and TNF-alpha and raised IL-10, and the effect was reversed by the PI3K inhibitor wortmannin. The methods are mostly written as intragastric dosing but one sentence says intraperitoneal, so the route in this study is not stated consistently.
Rat sciatic nerve transection and repairMale Lewis rats, 6 to 8 per group across 10 experimental groups2-4 mg/kg body weightNot statedLocal hydrogel at the repair site, systemically by vein or abdomen, or into the gastrocnemius muscleFunction followed to 16 weeks after repairNot applicableAnnals of Medicine and Surgery (PubMed Central)2021
Motor function measured by walking footprint grades improved significantly at 8 to 16 weeks when Dihexa or G-CSF was given into the muscle alongside mesenchymal stem cells, and foot flexion contractures were reduced. Sensory recovery was similar across all groups, and Dihexa was not tested on its own against vehicle in a way that separates its contribution.
Huntington's disease model in rats (negative result)40 male Wistar rats randomised to vehicle, 3-nitropropionic acid, or 3-nitropropionic acid plus DihexaNot stated in the report; 40 rats were split across 3 groupsNot statedNot stated in the report5 weeksNot applicableJournal of Huntington's Disease (PubMed)2024
Dihexa, named here by its code PNB-0408, did not protect rats from the weight loss, spatial learning deficits or motor dysfunction caused by the mitochondrial toxin. This is a published negative result in the same compound class that produced the memory findings, and the authors call for work in other models.
Community-reported4 rows
Vendor capsule product5 mg per capsule, 60 capsules per bottle (300 mg total)Not statedOral capsuleNot statedCommunity resource2026
This is a vendor claim about what ships, not a protocol. The listing publishes a per-lot certificate: lot 060526 was reported at 99.90 percent purity by HPLC with 5.36 mg measured against a 5 mg label. The page states plainly that the product is not for human, veterinary or food use.
Vendor nasal spray kit100 mcg per spray, about 100 sprays per 10 mL bottle (10 mg total)Not statedIntranasal, supplied pre-mixed with no reconstitutionNot statedCommunity resource2026
The aerosol listing is the reason this compound has nasal-spray support in the calculator. The lot certificate reports identity confirmed and 0.1 mg measured against a 100 mcg label. No published study has given Dihexa intranasally to any species, so the route here is a product format rather than a studied one.
Sources for this section (12)
  1. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agentsJournal of Pharmacology and Experimental Therapeutics (PubMed)2013Preclinical
  2. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system (RETRACTED)Journal of Pharmacology and Experimental Therapeutics (PubMed)2014Preclinical
  3. AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling PathwayBrain Sciences (PubMed Central)2021Preclinical
  4. Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair modelAnnals of Medicine and Surgery (PubMed Central)2021Preclinical
  5. Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in RatsJournal of Huntington's Disease (PubMed)2024Preclinical
  6. Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studiesNeuroscience and Biobehavioral Reviews (PubMed Central)2018Preclinical

Plus 6 community resources (dosing guides, forum threads and vendor write-ups), reported above but not linked.

Overview

Dihexa is a synthetic analogue of angiotensin IV, built at Washington State University by cutting the parent peptide down to its Tyr-Ile core and capping both ends so the molecule survives digestion and reaches the brain. It has been tested only in rats, mice, zebrafish and cell culture, where it is reported to act on the hepatocyte growth factor and c-Met system and to restore memory in scopolamine-treated and aged animals. No human study of Dihexa has ever been registered, the 2014 paper that established its mechanism was retracted in 2025, and vendors sell it both as oral capsules and as a pre-mixed nasal spray for research use only.

What researchers are exploring

These themes describe recurring questions in published research. They are not claims of effectiveness or recommendations for use.

  • 1

    Cognitive & neural

    Neuroplasticity, cognition, stress and sleep models.

  • 2

    Original oral dose-finding in rat dementia models

    This is the paper that first described Dihexa, reporting that the modified tripeptide core stayed active by mouth, reversed scopolamine-induced water-maze deficits and increased hippocampal synaptogenesis. The record.

  • 3

    APP/PS1 Alzheimer-model mice

    Both amounts shortened water-maze escape latency, raised neuronal counts and synaptophysin, lowered IL-1 beta and TNF-alpha and raised IL-10, and the effect was reversed by the PI3K inhibitor wortmannin. The methods.

  • 4

    Rat sciatic nerve transection and repair

    Motor function measured by walking footprint grades improved significantly at 8 to 16 weeks when Dihexa or G-CSF was given into the muscle alongside mesenchymal stem cells, and foot flexion contractures were reduced..

  • 5

    Huntington's disease model in rats (negative result)

    Dihexa, named here by its code PNB-0408, did not protect rats from the weight loss, spatial learning deficits or motor dysfunction caused by the mitochondrial toxin. This is a published negative result in the same.

  • 6

    Vendor capsule product

    This is a vendor claim about what ships, not a protocol. The listing publishes a per-lot certificate: lot 060526 was reported at 99.90 percent purity by HPLC with 5.36 mg measured against a 5 mg label. The page states.

What the current evidence can support

Study models remain visible so laboratory and animal findings are not mistaken for established human outcomes.

  • Animal

    Preclinical models

    4 protocol rows describe animal, cell or toxicology work. Amounts from these rows do not translate to people.

  • Not graded

    Community-reported use

    4 rows record what blogs, vendor write-ups or forums describe for Dihexa. None has been verified against primary literature.

Chemistry identifiers

Sequence, synonyms and registry identifiers as recorded in PubChem, the National Library of Medicine's open chemistry database. Formula, mass and CAS number are summarized at the top of the page.

Also listed as

PNB-0408, ATH-1001, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, Hexanoyl-Tyr-Ile-Ahx-NH2, UNII 9WYX65A5C2, DTXSID701032895

InChIKey

XEUVNVNAVKZSPT-JTJYXVOQSA-N

IUPAC name

(2S,3S)-N-(6-amino-6-oxohexyl)-2-[[(2S)-2-(hexanoylamino)-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanamide

Limitations and unknowns

Important limitations

  • Every amount on this page is a report of what a source describes, not a protocol to follow.
  • Preclinical and community rows do not establish a human amount, schedule or route.
  • Formulation, purity and presentation vary by supplier and are not covered by the dossier.

Sources

7 curated references, each with its journal, year and study model, plus 6 community resources reported but not linked.

  1. Dihexa (PubChem CID 129010512)PubChem, National Library of Medicine2026Not graded
  2. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agentsJournal of Pharmacology and Experimental Therapeutics (PubMed)2013Animal
  3. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system (RETRACTED)Journal of Pharmacology and Experimental Therapeutics (PubMed)2014Animal
  4. AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling PathwayBrain Sciences (PubMed Central)2021Animal
  5. Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair modelAnnals of Medicine and Surgery (PubMed Central)2021Animal
  6. Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in RatsJournal of Huntington's Disease (PubMed)2024Animal
  7. Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studiesNeuroscience and Biobehavioral Reviews (PubMed Central)2018Animal