Scientific Reference
Dihexa
Evidence profile: Predominantly preclinical
Dihexa is a small-molecule analogue of angiotensin IV, studied in animal and cell models of cognition, hair-cell damage and nerve repair. Its published structure is not a simple peptide chain but a two-residue core carrying a hexanoyl group at one end and an aminohexanoic amide at the other. Much of the founding work came from a single laboratory, and two of those papers now carry a retraction and an expression of concern. Later studies by other groups used zebrafish, rats and mice, and one of them reported no protective effect in its model.
Mechanism of Action
Published work describes dihexa as acting on the hepatocyte growth factor system rather than on an angiotensin receptor. In zebrafish lateral line hair cells, protection against aminoglycoside damage was attenuated by an HGF antagonist and by inhibitors of Akt, TOR and MEK, which the authors read as evidence that c-Met signalling is involved. A 2021 study in APP/PS1 mice attributed its effects to the PI3K and AKT pathway. The 2014 paper that first proposed direct HGF binding has since been retracted, so this account rests on the later work.
Molecular Information
- Type: Peptidomimetic
- Molecular weight: 504.7 g/mol
- Molecular formula: C27H44N4O5
- CAS: 1401708-83-5