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EmergingResearch compoundLimited evidence

Dihexa

Angiotensin IV analog, HGF/c-Met agonist, hippocampal synapse builder.

NootropicPeptideMemoryNeuroprotectionBDNFBDNFGlutamate
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Pharmacology

ClassPeptide · Memory · Neuroprotection · BDNF
Primary targetHGF / c-Met superagonist
Targets3 receptor targets
EvidenceLimited evidence
Affected systemsBDNFGlutamate

Contents

WHAT IS DIHEXA?

Detailed overview

Dihexa (N-hexanoyl-Tyr-Ile-(6) aminohexanoic amide, PNB-0408) is a metabolically stabilized small-molecule derivative of the Angiotensin IV peptide developed at Washington State University by Joseph Harding`s group. Preclinical evidence (PMC4201273): nearly 3× increase in hippocampal dendritic spine density, activation of PI3K/Akt, mTOR, ERK/MAPK, CREB and PSD-95 synaptic pathways. BBB passage is excellent (PMID 29733881); animal models show improvement in spatial working memory and long-term memory. A protective effect on hair cells is also described. Mechanism dispute: the originally proposed HGF/c-Met agonist profile was revisited after the Athira / Leen Kawas data-fraud scandal – the exact site of action remains unclear, but the synaptogenic activity is replicably documented. Take with fats (lipid-soluble), typical dose 5-10 mg sublingual/oral. No human clinical trials.

Mechanism

HGF/c-Met receptor agonist

Half-life

No human data

Legal status

Investigational, not approved

Receptor profile

  • HGF / c-Met receptorStrong
  • PI3K/Akt pathwayStrong
  • MAPK/ERK pathwayStrong

Safety

Side effects, stop signs, contraindications

Side effects · 5

  • No published human safety data; the side-effect profile in humans is essentially unknown, only preclinical and anecdotal reports exist.
  • Theoretical tumor and angiogenesis risk: HGF/c-Met pathway activation is a known cell-proliferation and angiogenic signaling route, its long-term human effect is uncharacterized.
  • Appetite suppression according to some user reports.
  • Overdose risk from extreme potency: estimated potency is many times that of BDNF, so even a small dosing error may trigger a disproportionate biological effect.
  • Unknown long-term safety; the consequences of chronic synaptogenic signaling in humans are not known.

Contraindications · 5

  • Active or prior malignancy, or elevated cancer risk: avoid due to the proliferative and angiogenic action of the c-Met/HGF pathway.
  • Pregnancy and breastfeeding: no safety data, the effect of growth-factor signaling on fetus/infant is unknown, avoid.
  • No human approval: not an approved drug anywhere, purely an experimental research chemical; use without medical supervision is not advised.
  • Undefined drug interactions: human half-life and metabolism are unknown, so the risk of co-administration with other agents cannot be estimated.
  • Diabetic retinopathy or other conditions involving pathological neovascularization: extra caution due to the theoretical angiogenic effect.

Related Nootropics

Same therapeutic category

FAQ

FAQ

Dihexa is an experimental research compound developed in a university lab with the goal of promoting growth of connections between brain cells (synapses), by mimicking a natural growth-factor signaling pathway. The available evidence is purely preclinical, meaning animal-study level, there is no human research or proven benefit, so it cannot be considered an established or safely used substance.

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Structure & chemistry

TypeNootropic
FormulaC26H41N5O5
UpdatedJune 19, 2026
MolekulaX Editorial Team·Source-verified · PubMed · FDA · EMA
Updated: June 19, 2026

The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.