Neurotrophic Research
Phase 1 Trials
Dihexa
Also known as: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, PNB-0408
Angiotensin IV-derived peptide. Studied in neurotrophic-signalling and synapse-formation research.
Research overview
Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, also called PNB-0408) is a small, chemically modified peptide derived from angiotensin IV, a fragment of the hormone angiotensin. It was designed by the Harding and Wright group at Washington State University to resist breakdown and reach the brain. Their rat studies reported better water-maze memory scores in rats given scopolamine (a drug that disrupts memory) and in aged rats (McCoy et al., J Pharmacol Exp Ther 2013). That paper has carried a journal expression of concern since 2021, and the group's main paper on how dihexa works was retracted in 2025.
Other groups report mixed results: better water-maze scores in a mouse model of Alzheimer's disease (Sun et al., 2021), but no difference from untreated animals in a rat model of Huntington's disease (Wells et al., 2024). We found no published studies of dihexa in people. A different compound aimed at the same target, fosgonimeton, did not meet its main goals in a placebo-controlled trial in Alzheimer's disease. Whether the animal findings hold up, and long-term safety, are unknown. Supplied for laboratory research use only.
Mechanism of action
Dihexa was reported to bind hepatocyte growth factor (HGF) and to strengthen signalling through the HGF receptor, c-Met, with more dendritic spines and synapses in hippocampal nerve cells. This came from cell and animal studies by the developing group, and the key paper was retracted in 2025, so the mechanism should be treated as unconfirmed. An independent mouse study linked its effects to the PI3K/AKT signalling pathway.