Semax: ACTH(4-10) Analogue and the Cerebral Ischaemia Literature

Design and the missing hormonal activity

ACTH(4-10) is the fragment of adrenocorticotropic hormone associated with reported effects on attention and memory, distinct from the steroidogenic activity of the full hormone, which requires regions not present in the fragment.

The Pro-Gly-Pro extension, shared with Selank, slows enzymatic degradation. Notably, the Pro-Gly-Pro fragment itself appears to have activity: Medvedeva et al. (J Mol Neurosci, 2013) studied Semax and its C-terminal Pro-Gly-Pro fragment in parallel on VEGF family gene expression, which means the extension is not a pharmacologically inert stabiliser and complicates attributing effects to the full sequence.

The ischaemia gene expression literature

Dmitrieva et al. (Cell Mol Neurobiol, 2010) report that Semax and Pro-Gly-Pro activate transcription of neurotrophins and their receptor genes after cerebral ischaemia. BDNF and its receptor TrkB are the most frequently reported targets.

Medvedeva et al. (BMC Genomics, 2014) performed genome-wide transcriptional analysis in rat brain focal ischaemia, reporting effects on immune and vascular system genes. Genome-wide designs are more informative than targeted assays because they show the breadth of transcriptional change rather than only the genes chosen in advance.

Stavchansky et al. (Genes, 2022) and Filippenkov et al. (Biomedicines, 2024) continue this line, the latter on ACTH-like peptides compensating a disrupted gene expression profile a day after experimental stroke.

Outside the ischaemia model

Liu et al. (Br J Pharmacol, 2025) report that Semax targets the mu opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice. This is the most mechanistically specific recent result and comes from outside the traditional provenance, which makes it worth particular attention.

Magrì et al. (J Inorg Biochem, 2016) examine how N-terminal acetylation influences copper and zinc coordination and biological properties. Metal coordination is an underexplored dimension of this peptide given the histidine residue in its sequence.

Spirin et al. (2024) review the compound's place in therapy and rehabilitation of ischaemic stroke patients, reflecting its clinical use in some jurisdictions, though this review is published in Russian.