Angiotensin IV analog
Dihexa
PreclinicalAlso known as PNB-0408, N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide
A nootropic whose key mechanism paper has been retracted.
- Cited sources
- 4
- Human-tested claims
- 0 of 3
- Best evidence
- Tier 3 · Preclinical
- Status
- Research-only
An orally active, brain-penetrant analog of angiotensin IV developed as a cognitive enhancer. It reversed drug-induced memory deficits in rats and improved an Alzheimer's mouse model, but the paper tying it to the HGF/c-Met growth pathway was retracted in 2025 and the original rat study carries a journal Notice of Concern. There are no human data.
How it works
Dihexa is built from the three-residue core of angiotensin IV, capped and stabilized so it survives digestion and crosses the blood-brain barrier. Its developers attributed its synapse-building effect to activation of hepatocyte growth factor and its receptor c-Met; that specific claim now rests on a retracted paper. Independent work in mice points instead at PI3K/AKT signalling and reduced neuroinflammation.
Sequence: N-hexanoic-Tyr-Ile-(6)-aminohexanoic amideA capped tripeptide-like molecule: hexanoyl N-terminus, Tyr-Ile, and a 6-aminohexanoic amide C-terminus.
What it's studied for
One claim per card, each with its own tier and source. Tiers 1 and 2 are human data. Tiers 3 and 4 are not yet.
- [1]McCoy et al., 2013 (J Pharmacol Exp Ther)(opens in a new tab)
Reversed scopolamine-induced memory deficits and increased hippocampal synaptogenesis in rats (study now under a Notice of Concern).
Preclinical - [2]Sun et al., 2021 (Brain Sci)(opens in a new tab)
Restored spatial learning and reduced neuroinflammation in APP/PS1 Alzheimer's-model mice via PI3K/AKT signalling (independent group).
Preclinical - [3]Benoist et al., 2014 – retraction notice (J Pharmacol Exp Ther)(opens in a new tab)
The claim that its effects depend on HGF/c-Met activation rests on a paper retracted in 2025.
Emerging
Safety & limitations
No human safety data of any kind exist. If the proposed HGF/c-Met mechanism is real, it is a pathway that drives tumor growth and metastasis when over-activated, which is a serious theoretical concern for chronic use.
[3]Benoist et al., 2014 – retraction notice (J Pharmacol Exp Ther)(opens in a new tab)The originating group's foundational rat study was the subject of a 2021 journal Notice of Concern, which weakens the preclinical base the grey market relies on.
[4]Notice of Concern on McCoy et al., 2013 (J Pharmacol Exp Ther)(opens in a new tab)Regulatory & legal status
Never approved or entered human trials in any jurisdiction. Preclinical only, and sold in grey markets on the strength of rodent data.
[1]McCoy et al., 2013 (J Pharmacol Exp Ther)(opens in a new tab)Frequently asked
Is dihexa stronger than BDNF?
That popular claim comes from an in-vitro potency comparison in the developer's own work, part of a literature now under a Notice of Concern and a retraction. It has never been measured in a person.
Has dihexa been tested in humans?
No. Every result is from rats or mice. There is no pharmacokinetic, safety or efficacy data in people.
References
Written by Twenty Residues editorial. Medical review: pending; a named reviewer is being assigned.
Last updated October 1, 2026.
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Update history
- 2026-10-01 — Entry added.