Investigational / not FDA-approved

Dihexa

AngIV analogue / HGF mimetic (PNB-0408) — preclinical only; refuse nootropic glow.

Editorial review:

What evidence says

Evidence snapshot

This drawer marks papers. It is not a plan, a dose, or a source. A paper is a bounded report. It is not a protocol. Grades name the object. They are not a safety rating.

Identity lock. Dihexa (also PNB-0408, ATH-1001; N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide / Hexanoyl-Tyr-Ile-Ahx-NH2) is an orally active angiotensin IV analogue reported to facilitate HGF/c-Met signaling in procognitive preclinical models. PubChem CID 129010512; formula C27H44N4O5 / MW 504.7; CAS 1401708-83-5. Human clinical efficacy trials are absent from this pack. No approved indication. Off-label does not apply. There is no label to be off of. Refuse human nootropic glow. This drawer marks papers. It is not use advice.

Bottom line

Evidence is preclinical: synaptogenic / procognitive AngIV-analogue work (Benoist, McCoy), APP/PS1 mouse cognitive rescue, and secondary AngIV reviews. Refuse human nootropic glow from mouse memory papers.

Papers

Core AngIV analogue / HGF–c-Met procognitive preclinical

PMID 25187433 — Benoist 2014

Tested: procognitive and synaptogenic effects of angiotensin IV–derived peptides depending on HGF/c-Met activation (includes Dihexa-class agents).

Does not show: a human cognition RCT.

PMID 23055539 — McCoy 2013

Tested: evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents (preclinical).

Does not show: human Alzheimer’s disease approval.

PMID 34827486 — Sun 2021

Tested: AngIV-analog Dihexa rescuing cognitive impairment and recovering memory in APP/PS1 mice via PI3K/AKT framing.

Does not show: human AD efficacy.

PMID 38489193 — Wells 2024

Tested: effects of an angiotensin IV analog on 3-nitropropionic acid–induced Huntington’s disease–like symptoms in rats.

Does not show: a human HD trial for Dihexa.

PMID 25674052 — Uribe 2015

Tested: hepatocyte growth factor mimetic protecting lateral line hair cells from aminoglycoside exposure (Dihexa as HGF mimetic tool — non-CNS sensory model).

Does not show: human hearing or cognition outcomes.

Secondary reviews (AngIV class — not Dihexa-only RCTs)

PMID 29733881 — Ho 2018

Tested: systematic review of experimental studies on cognitive benefits of angiotensin IV and angiotensin-(1-7).

Does not show: completed human Dihexa Phase 3.

What is not established

Any human clinical efficacy for Dihexa. That mouse procognitive results equal consumer nootropic outcomes. Equivalence to Semax, Cerebrolysin, or other neuropeptides. Product identity of unlabeled research chemicals vs published PNB-0408. This drawer does not provide use advice, schedules, or sourcing.

Selected sources

25187433 23055539 34827486 38489193 25674052 29733881

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