Dihexa Capsules 10mg 30ct by Omnix Peptides — research-grade capsules

Dihexa Capsules 10mg

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Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide; developmental code PNB-0408) is a synthetic small oligopeptide derived from angiotensin IV (AngIV), engineered to overcome AngIV's limitations as a research tool by adding lipophilic modifications that confer oral bioavailability and blood-brain barrier permeability.

$120.00

SKU: OM-CAPS-DIHEXA-10MG Category:

Research goals: Cognitive & Focus

Description

Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide; developmental code PNB-0408) is a synthetic small oligopeptide derived from angiotensin IV (AngIV), engineered to overcome AngIV’s limitations as a research tool by adding lipophilic modifications that confer oral bioavailability and blood-brain barrier permeability. The compound was synthesized at Washington State University in the laboratory of Joseph W. Harding to test whether a stable, brain-penetrant AngIV analogue could recapitulate AngIV’s reported cognitive effects in mammalian models. Dihexa’s working mechanism centers on activation of the hepatocyte growth factor (HGF) and its receptor c-Met (the HGF/c-Met system), a growth-factor signaling axis with established roles in neural circuit formation and synaptic plasticity. Reading the disclosure block below before the published research summary is strongly recommended.

The cleanest peer-reviewed positive finding from a research group fully independent of the original developing laboratory comes from Sun et al. at China Pharmaceutical University and Nanjing First Hospital: oral Dihexa restored spatial learning and memory in the APP/PS1 transgenic mouse model of Alzheimer’s disease via the PI3K/AKT signaling pathway, reduced neuroinflammation, and preserved hippocampal synaptophysin expression (Sun et al., Brain Sciences 2021).1

Important Note on the Evidence Base — Documented Research Integrity Issues

This compound carries the heaviest evidence-base disclosure in this catalog. Researchers evaluating Dihexa should be aware of the following:

  • Retracted foundational paper. The 2014 paper by Benoist et al. in the Journal of Pharmacology and Experimental Therapeutics (which established Dihexa’s HGF/c-Met mechanism via Morris water maze rescue with HGF antagonist blockade) was the subject of an Expression of Concern in 2021 and was formally retracted in April 2025 by the publishing journal following investigation into image manipulation. The retraction is permanent and the paper should no longer be cited as evidence for the HGF/c-Met mechanism, although the underlying mechanism has been corroborated in subsequent independent work (e.g., Sun et al. 2021, cited below).
  • Expression of Concern, not retracted. The 2013 paper by McCoy et al. in the Journal of Pharmacology and Experimental Therapeutics (the original cognitive-effects paper showing scopolamine-induced spatial learning deficit reversal in rats) has been under formal Expression of Concern since September 2021. As of 2026, the paper has not been formally retracted, but the Expression of Concern remains in force.
  • Investigation findings. A special committee investigation by the relevant institutions found that Leen Kawas (first author on Benoist 2014, co-author on McCoy 2013, and at the time CEO of the biotech commercializing a Dihexa derivative) had altered images in her doctoral dissertation and at least four published research papers from the Harding laboratory between approximately 2008 and 2012. Washington State University subsequently revoked her Ph.D.
  • Commercial fraud settlements. Athira Pharma (formerly M3 Biotechnology), the WSU spinout founded to commercialize Dihexa-derivative compounds, paid approximately $4 million in a False Claims Act settlement in January 2025 after a whistleblower exposed concealment of the research misconduct from federal grant agencies, and approximately $10 million in a separate class-action settlement to investors. The company’s stock collapsed from a $17 IPO price (September 2020) to under $1.
  • Distinguishing Dihexa from fosgonimeton. Athira’s lead clinical candidate, fosgonimeton (formerly ATH-1017 / NDX-1017), is a structurally distinct phosphate prodrug of Dihexa — not Dihexa itself. Some clinical results commonly attributed to “Dihexa” in marketing or popular press are actually fosgonimeton results. Notably, fosgonimeton’s Phase 2/3 LIFT-AD trial in mild-to-moderate Alzheimer’s disease missed its primary endpoint in topline results released in 2023.
  • Independent literature is thin. A substantial fraction of Dihexa’s primary published evidence base originates from the Harding laboratory and direct collaborators. Fully independent peer-reviewed replication of Dihexa’s specific potency claims (including the widely cited 7 orders of magnitude more potent than BDNF figure from the original work) is limited. The Sun et al. 2021 Brain Sciences paper from China Pharmaceutical University and Nanjing First Hospital is the strongest fully independent positive finding identified for this product description; we have intentionally relied on it as the lead anchor for this reason.
  • No human clinical trials. No human clinical trials of Dihexa itself have been published in peer-reviewed literature as of 2026. All Dihexa-specific cognitive evidence is preclinical (cell culture and rodent). Human clinical work cited in popular press is generally fosgonimeton work, not Dihexa work.

Dihexa is not approved by the FDA or EMA. This product is for laboratory research only. We have chosen to disclose the above explicitly because researchers will encounter the retraction, the Athira/Kawas matter, and the fosgonimeton distinction during literature review — and we believe transparent disclosure serves the research community better than omission.

Published Research on Dihexa

Cognitive Rescue in APP/PS1 Alzheimer’s Mice — Sun et al., Brain Sciences (2021)

This study from China Pharmaceutical University and Nanjing First Hospital is the strongest positive Dihexa finding from a research group fully independent of the original Harding laboratory. The authors administered oral Dihexa to APP/PS1 transgenic mice (a standard amyloidopathy model of Alzheimer’s disease) and showed that brain AngIV levels were elevated relative to wild-type after Dihexa administration, that spatial learning and memory were restored on Morris water maze testing, that hippocampal neuronal density and synaptophysin protein expression were preserved, that astrocyte and microglial activation were reduced, and that pro-inflammatory cytokines (IL-1β, TNF-α) decreased while anti-inflammatory IL-10 increased. Mechanistic experiments using the PI3K inhibitor wortmannin demonstrated that PI3K/AKT signaling is required for the anti-inflammatory and anti-apoptotic effects, identifying the brain AngIV/PI3K/AKT axis as the proximate mechanism in this model.1

Original Procognitive Characterization — McCoy et al., Journal of Pharmacology and Experimental Therapeutics (2013)

This paper has been under Expression of Concern since 2021 (see disclosure block above). It is summarized here for completeness because subsequent work, including Sun et al. 2021 above, was framed against it. The McCoy et al. paper introduced Dihexa as a metabolically stabilized AngIV analogue and reported reversal of scopolamine-induced spatial learning deficits in rats and improved spatial learning in aged rats following oral administration. In hippocampal neuron cultures, Dihexa was reported to induce spinogenesis and synaptogenesis at picomolar concentrations — the basis for the widely-cited seven orders of magnitude more potent than BDNF potency figure. Researchers should weigh these claims with the caveat that this paper carries an active Expression of Concern.2

Otoprotection in Zebrafish Lateral Line Hair Cells — Uribe et al., Frontiers in Cellular Neuroscience (2015)

This paper from the Coffin laboratory (with WSU co-authors) tested whether Dihexa could protect zebrafish lateral line hair cells (homologous to mammalian inner ear hair cells) from aminoglycoside-induced ototoxicity. A Dihexa concentration of 1 μM conferred optimal protection from acute neomycin or gentamicin exposure. Dihexa did not alter aminoglycoside entry into hair cells but attenuated cell death through HGF-dependent intracellular signaling, with downstream contributions from the Akt, mTOR, and MEK pathways. The work supports the broader HGF/c-Met mechanism beyond the hippocampal cognitive context, and the zebrafish protection model has been further studied in subsequent work in mammalian systems.3

HGF/c-Met System Review — AlzForum / Wright & Harding, Progress in Neurobiology (2015)

This narrative review covers the development of small-molecule angiotensin IV analogues for Alzheimer’s and Parkinson’s diseases, with Dihexa as the lead candidate at the time of writing. The review situates Dihexa within the renin-angiotensin system’s central nervous system arm, summarizes the HGF/c-Met activation hypothesis, and surveys behavioral pharmacology in rodent cognitive models. Note that the senior author is Wright, the principal investigator of the Harding laboratory; the review is therefore not independent of the original developing group, and findings discussed in it should be evaluated together with the disclosures above.4

About the Compound

Dihexa is a small synthetic oligopeptide derived from the three N-terminal residues of angiotensin IV (Nle-Tyr-Ile), with structural modifications that block enzymatic degradation, increase lipophilicity, and confer oral bioavailability and blood-brain barrier permeability. The compound is a hexanoyl-Tyr-Ile core with a 6-aminohexanoic acid amide tail. Its working mechanism is allosteric facilitation of HGF/c-Met signaling: Dihexa binds HGF with high affinity (reported Kd ~65 pM in the original work) and is proposed to potentiate HGF dimerization and c-Met phosphorylation at subthreshold endogenous HGF concentrations. Downstream signaling involves PI3K/AKT, MAPK/ERK, and PLC-γ pathways, which are well-characterized drivers of synaptogenesis, dendritic spine maturation, and neuronal survival. Primary research applications include cognitive impairment models, HGF/c-Met signaling studies, and neurodegeneration research in rodent models.

  • Compound class: synthetic small oligopeptide; angiotensin IV analogue
  • Sequence (formal name): N-hexanoic-Tyr-Ile-(6) aminohexanoic amide
  • IUPAC name: 6-[(2S,3S)-2-[(2S)-2-hexanamido-3-(4-hydroxyphenyl)propanamido]-3-methylpentanamido]hexanamide
  • Synonyms: PNB-0408, Hexanoyl-Tyr-Ile-Ahx-NH2, MM-201 (older designation)
  • CAS Number: 1401708-83-5
  • Molecular Formula: C27H44N4O5
  • Molecular Weight: 504.66 g/mol
  • Solubility: slightly soluble in DMSO and methanol; commonly reconstituted in sterile water or buffer for research use
  • Mechanism (working): allosteric potentiation of HGF/c-Met signaling; activation of PI3K/AKT downstream pathway driving synaptogenesis and anti-apoptotic effects in hippocampus
  • Regulatory status: not approved by the FDA or EMA. No human clinical trials of Dihexa itself published as of 2026. Phase 2/3 trial of structurally distinct prodrug fosgonimeton (Athira ATH-1017) missed primary endpoint in 2023

Product Specifications

  • Format: capsules
  • Strength: 10 mg per capsule
  • Count: 30 capsules per bottle
  • Purity: ≥98% (HPLC verified)
  • Container: sealed amber bottle
  • Certificate of Analysis: lot-specific COA available

See the FDA Disclosure, Storage Instructions, and RUO tabs for handling, storage, and regulatory information.

References

  1. Sun X, Deng Y, Fu X, Wang S, Duan R, Zhang Y. AngIV-analog Dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via the PI3K/AKT signaling pathway. Brain Sci. 2021;11(11):1487. doi:10.3390/brainsci11111487
  2. McCoy AT, Benoist CC, Wright JW, et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013;344(1):141-154. doi:10.1124/jpet.112.199497 [Notice of Concern issued September 2021; not retracted as of 2026.]
  3. Uribe PM, Kawas LH, Harding JW, Coffin AB. Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure. Front Cell Neurosci. 2015;9:3. doi:10.3389/fncel.2015.00003
  4. Wright JW, Kawas LH, Harding JW. The development of small molecule angiotensin IV analogs to treat Alzheimer’s and Parkinson’s diseases. Prog Neurobiol. 2015;125:26-46. doi:10.1016/j.pneurobio.2014.11.004
  5. Retraction notice (Benoist et al. 2014): Benoist CC, Kawas LH, Zhu M, et al. 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;351(2):390-402. doi:10.1124/jpet.114.218735. RETRACTED April 2025. See retraction notice in J Pharmacol Exp Ther. 2025;392(4):103567.

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For research use only. Not for human consumption.