Peptide reference
Dihexa
Dihexa acetate ·PNB-0408 ·N-hexanoic-Tyr-Ile-(6) aminohexanoic amide ·Angiotensin-IV analog (Nle-Tyr-Ile-derived)
What cited sources report about Dihexa
Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide; also designated PNB-0408) is a synthetic angiotensin-IV-derived dipeptide-mimetic developed at Washington State University as an orally active, blood-brain-barrier-permeant procognitive candidate. The compound is currently slated for FDA Pharmacy Compounding Advisory Committee (PCAC) review at a meeting in February 2027 (exact date pending). As of the cited literature, Dihexa has no FDA-approved indication and no marketing authorization in any major jurisdiction. The summaries below report what individual cited sources state; this page does not assert claims beyond what those sources report.
McCoy et al. (2013) — Journal of Pharmacology and Experimental Therapeutics
The originating paper from the Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology at Washington State University described the chemical design pathway from the angiotensin-IV core (Nle-Tyr-Ile motif) to dihexa. The authors reported in-vitro stability gains, oral activity, blood-brain-barrier permeability, and reversal of scopolamine-induced Morris water maze deficits in aged-rat models. Readers should note the paper was subsequently flagged with an Expression of Concern in J Pharmacol Exp Ther (2021;378(3):313).
Subsequent chemical modifications, which were designed to increase hydrophobicity and decrease hydrogen bonding, yielded an orally active, blood-barrier permeant, metabolically stabilized analog, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (dihexa)…
Sun et al. (2021) — Brain Sciences
A preclinical study at China Pharmaceutical University and Nanjing Medical University administered Dihexa to APP/PS1 transgenic mice (an Alzheimer’s-disease genetic model) and measured Morris water maze performance, neuronal markers, and cytokine profiles. The authors reported that Dihexa-treated animals exhibited recovered spatial learning, increased synaptophysin expression, and reduced pro-inflammatory cytokines, and they discussed the PI3K/AKT pathway as a candidate mediating axis.
Dihexa restored spatial learning and cognitive functions in the Morris water maze test.
Wells et al. (2024) — Journal of Huntington’s Disease
A 2024 negative-result study from Whitworth University, OHSU, and the University of Washington administered PNB-0408 (Dihexa) alongside chronic 3-nitropropionic acid in Wistar rats as a model of Huntington’s-disease-like neurotoxicity. The authors reported that, in contrast to prior Alzheimer’s-disease-relevant preclinical findings, Dihexa did not attenuate 3-NP-induced motor or cognitive deficits in this paradigm — a useful counterweight in the cited literature.
From our observations and analysis, PNB-0408 did not protect rats from the deficits induced by 3-NP neurotoxicity. … Our findings suggest that PNB-0408 may not be an efficacious treatment strategy for preventing 3-NP-induced HD-like symptoms in a preclinical model.
PubChem — Dihexa
The PubChem compound entry/search results for Dihexa catalogue the N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide structure and aggregate synonym sets (including PNB-0408) with links to the underlying chemical literature.
Coverage notes
Coverage notes: limited primary literature available as of last_updated date. The PubMed Dihexa-specific record set is small (the search “Dihexa AND angiotensin IV” returned only seven results), and the originating 2013 paper was flagged with a 2021 Expression of Concern (J Pharmacol Exp Ther 2021;378(3):313) — readers should weigh that downstream context when interpreting subsequent preclinical claims that cite it. There are no completed Phase II/III clinical efficacy trials of Dihexa indexed on ClinicalTrials.gov, and no FDA-approved indication exists. This page will be updated when the February 2027 PCAC briefing materials are released.