Dihexa
PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide
An angiotensin IV derivative that binds hepatocyte growth factor with picomolar affinity and grows dendritic spines in rodent brains. No human has ever been studied taking it.
Preclinical only
Not approved anywhere and never entered human trials. A university drug discovery compound sold online as research material.
What it is
Dihexa is a small peptidomimetic derived from angiotensin IV, developed at Washington State University as a candidate treatment for Alzheimer's disease. It binds hepatocyte growth factor with extraordinarily high affinity, reported in the picomolar range, and through that activates the c-Met receptor.
In cultured hippocampal neurons it increases dendritic spine density substantially. In rodent models of Alzheimer's and chemically induced amnesia it crosses the blood brain barrier and restores performance on spatial learning tasks.
The preclinical potency is genuinely remarkable, and that is the whole of the story.
There is no human data at all
Not a phase 1. Not a safety study. Not a pharmacokinetic characterisation. As of now there is no completed or ongoing human efficacy trial for dihexa in the published literature or in trial registries. Every cognition result comes from rodent and zebrafish models.
The doses circulating in online protocols are extrapolations from animal studies, which is not a valid way to arrive at a human dose for a novel compound with an unknown therapeutic index.
The mechanism is the reason for caution, not the reason for enthusiasm
c-Met is a receptor tyrosine kinase. Its dysregulation is one of the better-characterised drivers of tumour growth, invasion and metastasis across many human cancers, and a substantial part of oncology drug development is devoted to inhibiting it.
Dihexa activates it, potently and systemically, in a person with no monitoring and no dose rationale.
That is not a hypothetical objection dragged in to sound cautious. It is the same pathway, in the same direction, that oncologists spend their careers trying to shut down. A compound this potent at a receptor this consequential is exactly the sort of thing that needs a phase 1 before anyone swallows it, and it has not had one.
Practical notes
- Preclinical potency is not a safety argument, it is the opposite. The more powerfully a compound acts on a growth pathway, the more a human safety study matters before use.
- This is a research tool that escaped the laboratory. It was never a product, and nobody involved in developing it proposed that healthy people take it for focus.
- The absence of side effect reports means nothing here. Growth pathway effects do not announce themselves within a few weeks.
Side effects and warning signs
Commonly reported
- Unknown in humans. No clinical safety study of any kind has been conducted
- Headache and irritability are the most common self-reports, from an unverified base
Stop and get medical help
- Any active or suspected malignancy. The c-Met pathway this compound activates is one of the most frequently dysregulated oncogenic pathways in human cancer
- Any unexpected neurological symptom, since there is no baseline for what this compound does in a person
Sources
From the community
Discussion for this compound concentrates in r/Nootropics.
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