Dihexa vs Semax

Dihexa

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.

Semax

Semax is a synthetic seven-residue peptide, Met-Glu-His-Phe-Pro-Gly-Pro, built from a short fragment of adrenocorticotropic hormone (ACTH). Its first four residues match positions 4 to 7 of ACTH; the Pro-Gly-Pro tail does not occur there in the hormone and is reported to slow breakdown by peptidases. Short ACTH fragments of this kind are described as lacking the steroid-releasing activity of the full hormone. Semax was developed by Russian researchers, and most of its literature comes from Russian groups working in rats and cell cultures. Controlled human studies are few, many are published only in Russian, and independent replication elsewhere is limited.

How Dihexa acts

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 The 2014 paper that first proposed direct HGF binding has since been retracted, so this account rests on the later work.

How Semax acts

No specific receptor for Semax has been identified. Studies in rats have reported higher expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus, and other work has examined dopamine and serotonin turnover in the striatum. Transcriptome studies in rat models of cerebral ischaemia describe shifts in the expression of genes tied to immune and vascular processes. Because its core derives from ACTH, an interaction with melanocortin receptors has been proposed, though direct binding evidence is limited. How these separate observations connect has not been worked out.

The records side by side

• Type: Dihexa, Peptidomimetic; Semax, Synthetic ACTH analog (heptapeptide)
• Length: Dihexa, not recorded; Semax, 7 amino acids
• Molecular weight: Dihexa, 504.7 g/mol; Semax, 813.9 g/mol
• Molecular formula: Dihexa, C27H44N4O5; Semax, C37H51N9O10S

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.