Semax

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide developed at the Institute of Molecular Genetics of the Russian Academy of Sciences as an analogue of ACTH(4-10) — the core neuropeptide pharmacophore of adrenocorticotropic hormone that retains cognitive and neuroprotective activities without adrenocortical stimulation. Registered as a pharmaceutical in Russia for cerebrovascular and cognitive indications, Semax is classified as a research compound outside Russia and is supplied by Signal Labs for laboratory and analytical research purposes only.

ACTH(4-10) (Met-Glu-His-Phe-Arg-Trp-Gly) was established in the 1970s-80s by de Wied and colleagues as the minimal ACTH fragment with cognitive, learning, and memory enhancement properties — distinct from the adrenocortical-stimulating activity that requires the full 1-24 amino acid sequence. Semax was designed by replacing Arg-Trp-Gly with Pro-Gly-Pro: the Arg-Trp dipeptide at positions 6-7 was replaced by Pro at position 5 (present in ACTH(4-10) at position 6, retained in Semax at position 5), and the Gly at position 7 was extended with Pro-Gly-Pro for stability purposes. The resulting heptapeptide retains the ACTH-like neurobiological properties of the parent pharmacophore while having improved metabolic stability through the Pro-Gly-Pro C-terminal carboxypeptidase-resistant extension.

BDNF (brain-derived neurotrophic factor) and TrkB receptor biology is Semax's most extensively published research theme. Manchenko et al. (Journal of Neurochemistry, 2012) demonstrated that Semax administration to rats increased BDNF mRNA expression in the hippocampus and altered BDNF gene promoter methylation — connecting Semax to both neurotrophic signalling and epigenetic gene regulation. BDNF/TrkB signalling through PI3K/Akt and MAPK/ERK cascades underlies LTP (long-term potentiation), hippocampal neurogenesis, synaptic plasticity, and neuroprotection under stress conditions.

Dopaminergic system research with Semax has examined effects on dopamine transporter (DAT) expression by immunohistochemistry and Western blot in striatal tissue, D1R and D2R receptor density by radioligand binding, and tyrosine hydroxylase (TH) expression as the rate-limiting dopamine synthesis enzyme. Dopamine system interactions are relevant given ACTH(4-10)'s established connections to catecholamine signalling.

Neuroprotection research has placed Semax in hypoxia, excitotoxicity (glutamate-induced), and ischaemia model contexts. Stavchansky et al. (Journal of Peptide Science, 2015) examined Semax alongside its Pro-Gly-Pro component in rat focal ischaemia models, demonstrating maintenance of BDNF and other neurotrophic factor expression — suggesting neuroprotection through neurotrophic support maintenance rather than direct anti-excitotoxic mechanisms.

HIF-1alpha pathway research has examined whether Semax influences hypoxia-inducible factor 1-alpha expression and target gene activation (VEGF, GLUT1, EPO) under hypoxic conditions — a mechanism relevant to the ischaemia neuroprotection biology.

Research assay design: for gene expression studies requiring 12-24 hour incubation periods, consider NA Semax Amidate (available separately) for improved stability. For acute receptor pharmacology (less than 4 hours), standard Semax is appropriate. Working concentrations: nanomolar to low micromolar range for most published in vitro research.

MW: approximately 887 g/mol. CAS: 80714-61-0. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.

For dopaminergic research with Semax: use primary rat striatal neurons (embryonic day 17-18, culture until DIV14-21) or the SH-SY5Y dopaminergic-like cell line differentiated with retinoic acid (10uM, 5 days). Treat with Semax (1nM-1uM) for 48-72 hours. Measure: DAT (SLC6A3) mRNA by qRT-PCR; DAT protein by Western blot (MAb16, Millipore) and surface expression by flow cytometry; TH (tyrosine hydroxylase, rate-limiting dopamine synthesis enzyme) by Western blot; and dopamine content by HPLC-ECD in cell lysate. For neuroprotection research: apply Semax (1-100nM, 1 hour pre-treatment) before neurotoxic challenge (6-OHDA 50uM for dopaminergic toxicity; glutamate 100uM for excitotoxicity) and measure cell viability (MTT, LDH release), apoptosis (annexin V/PI), and BDNF protein by ELISA at 24-48 hours. MW: approximately 887 g/mol. CAS: 80714-61-0. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.