Dihexa

Dihexa is a small-molecule research chemical, not a peptide, with the chemical name N-hexanoic-Tyr-Ile-(6) aminohexanoic amide and the developmental code PNB-0408. Its molecular formula is C27H44N4O5, its molecular weight is 504.7 g/mol, its CAS number is 1401708-83-5, and its PubChem CID is 129010512. The structure is a hexanoylated tyrosine joined to isoleucine and capped with a 6-aminohexanoic amide. That short, doubly capped framework is why the literature classifies it as a peptidomimetic, a molecule built to reproduce a peptide interaction without being one. It is supplied here in a solid unit-dose format for laboratory research use only.

Dihexa is an analogue of angiotensin IV, the hexapeptide fragment Val-Tyr-Ile-His-Pro-Phe generated within the renin-angiotensin system. The N-terminal hexanoyl chain and the C-terminal amide cap were introduced to raise hydrophobicity and to reduce susceptibility to aminopeptidase and carboxypeptidase cleavage, properties the parent fragment lacks. Dihexa also carries the code ATH-1001 from the programme at M3 Biotechnology, later Athira Pharma, the Washington State University spin-out formed around this chemical series. It holds no regulatory approval in any jurisdiction, and it is frequently filed alongside peptide reference material, which its structure does not support.

Dihexa originated in a Washington State University programme led by Joseph Harding and John Wright that began with angiotensin IV pharmacology in rodents and moved toward smaller, metabolically stabilised analogues. Benoist and colleagues first described the compound in 2011 in hippocampal synaptogenesis assays and rodent spatial-learning models (PubMed 21719467).

Wright, Kawas and Harding reviewed the analogue series and the hepatocyte growth factor hypothesis in 2015 (PubMed 25455861). Ho and Nation published an independent systematic review of experimental angiotensin IV studies in 2018 (PubMed 29733881).

The evidence base is narrow, preclinical and partly compromised. A foundational 2014 paper on the hepatocyte growth factor and c-Met mechanism was retracted in April 2025 (PubMed 40312093), and a 2013 analogue paper carries an active Notice of Concern (PubMed 34551989). Verify the standing of any source before relying on it.

The mechanism most often attributed to Dihexa is potentiation of hepatocyte growth factor signalling at the receptor tyrosine kinase c-Met, a pathway associated with dendritic branching and synapse formation. This remains a hypothesis, and the direct biochemical evidence for it is weakened by the 2025 retraction noted above.

Two distinctions are useful. Despite its angiotensin lineage, Dihexa is not reported to act at the AT1 or AT2 receptors, and the AT4 site of its parent fragment, insulin-regulated aminopeptidase, is not the mechanism now proposed for it. Dihexa is also not a peptide, so comparison with Semax or Selank is by research context, not structure.

A methodology caveat applies. The record is built from primary neuronal cultures, binding assays and rodent behavioural paradigms, so reported effects belong to the assay used.

Sealed Dihexa reference material is stored cool, dry and shielded from light, with freezer storage at -20°C conventional for small-molecule standards. No duration is given here: the stability window for a batch is documented on its Certificate of Analysis.

Small molecules of this class are generally less thermolabile than peptides, but the amide-rich structure is hygroscopic, meaning it takes up atmospheric moisture, which affects weighed accuracy. Capsules are held as printed on the product label.

Reconstitution is the term for returning a solid compound to solution; this page defines the term and gives no procedure. Dihexa sits in the small-molecule solubility class, with limited aqueous solubility and DMSO the general in vitro solvent class for such compounds.

Solid material is handled in low humidity with minimal open-container exposure. Preparation parameters belong to the published methodology being reproduced, read alongside the Certificate of Analysis for the lot.

Identity and purity for a small molecule are established by high-performance liquid chromatography with ultraviolet detection and by liquid chromatography with mass spectrometry. The primary identity check is a mass consistent with 504.7 g/mol and a formula matching C27H44N4O5. Verified purity is documented per lot on the Certificate of Analysis.

Stereochemistry matters here. The tyrosine and isoleucine centres are defined as (2S) and (2S,3S), and diastereomeric impurities are not resolved by mass alone. Novelle Bio and Catalyst Compounds material is batch tested with a published COA.

Dihexa is catalogued with compounds studied in central nervous system models, most of which are peptides while it is not.

• Semax.
  A synthetic ACTH(4-10) analogue studied in rodent central nervous system models, a research-context comparator, not a structural relative.
• Selank.
  A tuftsin analogue investigated in animal models of anxiety-related behaviour, a second peptide comparator.
• Epitalon.
  A synthetic tetrapeptide investigated in animal models for pineal and telomere-associated pathways, a separate mechanism.
• P21.
  A ciliary neurotrophic factor derived peptidomimetic, the closest parallel to Dihexa as a designed mimetic.
• N-Acetyl Semax and N-Acetyl Selank (entries forthcoming). Acetylated variants of the two peptides above, studied as stability-modified forms.

Benoist CC, Wright JW, et al. (2011). Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs. J Pharmacol Exp Ther.
PubMed 21719467

Wright JW, Kawas LH, Harding JW (2015). The development of small molecule angiotensin IV analogs to treat Alzheimer’s and Parkinson’s diseases. Prog Neurobiol.
PubMed 25455861

Ho JK, Nation DA (2018). Cognitive benefits of angiotensin IV and angiotensin-(1-7): a systematic review of experimental studies. Neurosci Biobehav Rev.
PubMed 29733881

Sun X, Deng Y, et al. (2021). AngIV-analog Dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via the PI3K/AKT signaling pathway. Brain Sci.
PubMed 34827486

Dihexa is stocked in one format, capsules, from two house brands at a listed 10mg strength. There is no vial or liquid spray listing for this compound at present. The strengths shown are product specifications, not amounts to administer. Each lot is batch tested with a published Certificate of Analysis carrying verified purity and identity data.

• Browse all Dihexa research products
• Catalyst Compounds Dihexa Capsules, 10mg
• Novelle Bio Dihexa Capsules, 10mg
• Collections: Capsules & Tablets. Documentation: COA and Lab Testing.

These products are sold for Research Use Only and are not intended for human consumption.