Semax

The overview

What is Semax?

Semax is a synthetic heptapeptide combining the ACTH(4-7) fragment (Met-Glu-His-Phe) with a C-terminal Pro-Gly-Pro tripeptide that confers resistance to aminopeptidase cleavage, prolonging in-vitro and ex-vivo stability relative to native ACTH(4-10). In receptor-binding assays on rat basal forebrain membranes, tritium-labeled Semax shows specific, reversible, time-dependent binding with a dissociation constant in the low-nanomolar range. At the signaling level, ex-vivo and cell-model studies report rapid up-regulation of brain-derived neurotrophic factor (BDNF) protein and exon-specific BDNF mRNA, together with increased tyrosine phosphorylation of the TrkB receptor, implicating downstream neurotrophin-receptor cascades (e.g., MAPK/ERK and PI3K/Akt). Semax lacks the corticotropic N-terminal ACTH residues, so it is described as devoid of classical adrenal-stimulating hormonal activity. Additional reported actions in rodent neurochemical models include modulation of dopaminergic and serotonergic systems and transcriptional regulation of neurotrophins and their receptor genes. These observations frame Semax as a melanocortin-derived modulator of neurotrophin signaling in preclinical systems.

In the research

Where Semax shows up

The areas researchers focus on with Semax - and why it has the science community paying attention.

• BDNF/TrkB neurotrophin receptor signaling in rodent hippocampus and basal forebrain (ex-vivo/cell models)
• Melanocortin/ACTH-fragment receptor-binding characterization
• Neurotrophin and receptor gene transcription in cerebral ischemia models
• Monoaminergic (dopaminergic/serotonergic) system modulation in rodent neurochemical assays
• Peptide enzymatic-stability and degradation kinetics in vitro

By the numbers

The facts that matter

To the molecule

Molecular specifications

Sourced, not claimed

The science behind it

The peer-reviewed studies behind Semax, linked so you can read them yourself.

1. Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Dubynina EV, Antonova LV, Kamensky AA, Grivennikov IA, Myasoedov NF, et al. (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus Brain Research.

   “A single application of Semax (50 microg/kg body weight) results in a maximal 1.4-fold increase of BDNF protein levels accompanying with 1.6-fold increase of trkB tyrosine phosphorylation levels, and a 3-fold and a 2-fold increase of exon III BDNF and trkB mRNA levels, respectively, in the rat hippocampus.”

   DOI ↗PubMed ↗
2. Dolotov OV, Karpenko EA, Seredenina TS, Inozemtseva LS, Levitskaya NG, Zolotarev YA, Kamensky AA, Grivennikov IA, Engele J, Myasoedov NF (2006). Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain Journal of Neurochemistry.

   “The binding of tritium-labelled Semax was found to be time dependent, specific and reversible, with a mean dissociation constant (KD) of 2.4 +/- 1.0 nM and a BMAX value of 33.5 +/- 7.9 fmol/mg protein.”

   DOI ↗PubMed ↗
3. Dmitrieva VG, Povarova OV, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV (2010). Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia Cellular and Molecular Neurobiology.

   “We have shown for the first time that both Semax and PGP activate the transcription of neurotrophins and their receptors in the cortex of rats subjected to pMCAO.”

   DOI ↗PubMed ↗
4. Medvedeva EV, Dmitrieva VG, Povarova OV, Limborska SA, Skvortsova VI, Myasoedov NF, Dergunova LV (2014). The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis BMC Genomics.

   “In conditions of rat brain focal ischemia, Semax influenced the expression of genes that promote the formation and functioning of the vascular system.”

   DOI ↗PubMed ↗

Straight answers

Questions, answered