Dihexa

Developed at Washington State University (Harding and Wright) from the brain peptide angiotensin IV, then commercialized by M3 Biotechnology, later Athira Pharma. Its relative fosgonimeton, described as a phosphate prodrug of Dihexa, reached human trials.

Binds hepatocyte growth factor (HGF) and increases signaling through its receptor c-Met. In rats, blocking HGF canceled its memory effect, supporting this pathway. It seemed to matter mainly in injured or impaired brains.

Rat studies reported that it restored water-maze performance in chemically impaired rats by several routes, helped aged rats less consistently, nearly tripled dendritic spines in cultured neurons and crossed the blood-brain barrier. No human study of Dihexa has been published. Its relative fosgonimeton missed its main goals in two Alzheimer's trials (2022 and 2024). The widely repeated "10 million times more potent than BDNF" figure came from a press release, not a direct comparison.

Human safety is unknown. The main theoretical concern is cancer: c-Met drives growth and spread of many cancers, and Dihexa has no long-term toxicity data. Rat half-life was very long (about 9–13 days), so any effect could persist. Fosgonimeton trials mainly showed injection-site reactions.

Never tested in humans and not approved anywhere. FDA lists an earlier compounding nomination as withdrawn, noting no human exposure data, so it is not compoundable; it is reportedly scheduled for FDA advisory committee review by early 2027. Not named by WADA but treated as prohibited at all times under S0 or S2 (HGF modulators).