Semax: Chemistry Profile & Research Overview

What Is Semax?

Semax is a synthetic heptapeptide assigned CAS number 80714-61-0. It is derived from a fragment of adrenocorticotropic hormone (ACTH) — specifically the N-terminal residues 4 through 7 — with a C-terminal Pro-Gly-Pro tripeptide extension. The full sequence is Met-Glu-His-Phe-Pro-Gly-Pro. The Pro-Gly-Pro extension — the same C-terminal motif used in the related regulatory peptide Selank — confers resistance to enzymatic degradation in research matrices. As a research-grade synthetic peptide, Semax is used in vitro and in non-human systems as a model substrate in peptide-stability research, in solid-phase peptide synthesis (SPPS) methodology studies, and as a reference compound in short-peptide pharmacology screens.

Chemical Properties

Historical Development and Discovery

The Semax sequence was developed in the late 1980s by researchers at the Institute of Molecular Genetics in Moscow as part of a structure-activity research program investigating short, stabilized ACTH-derived peptides. Native ACTH(4-10) (Met-Glu-His-Phe-Arg-Trp-Gly) had been characterized as a fragment with research-relevant binding behavior, but its short biochemical half-life in research models — driven by rapid proteolytic cleavage — limited its experimental utility. Investigators truncated the fragment to the first four residues (Met-Glu-His-Phe) and appended a C-terminal Pro-Gly-Pro extension, which had previously been shown to stabilize short peptides against enzymatic degradation. The resulting heptapeptide entered the chemical literature as Semax and has since become a standard reference compound in stabilized-peptide methodology research and in the broader study of Russian-developed regulatory peptides.

Chemical Architecture and Structural Features

The Pro-Gly-Pro Stabilization Motif

The defining structural feature of Semax is the C-terminal Pro-Gly-Pro tripeptide extension, identical to the motif used in Selank. Proline residues bracketing a central glycine adopt a constrained rigid conformation that blocks recognition by common exopeptidases. The Pro-Gly-Pro motif is itself a recognized bioactive fragment in the chemical literature, and its inclusion as a C-terminal extension is a well-established strategy for designing short stabilized peptides.

The ACTH(4-7) Pharmacophore

The N-terminal Met-Glu-His-Phe segment is the conserved pharmacophore of the ACTH(4-10) fragment, containing the residues required for receptor engagement in published in vitro work. By preserving this four-residue head while adding the stabilizing tail, Semax retains the binding profile of the parent fragment while resisting enzymatic inactivation.

Solid-Phase Synthesis Considerations

Semax is typically produced by Fmoc-based solid-phase peptide synthesis (SPPS) followed by RP-HPLC purification. The 7-residue length and absence of cysteine residues simplify the synthesis. Common challenges discussed in the synthesis literature include methionine oxidation during global deprotection (addressed via scavenger strategies) and incomplete coupling at the sterically constrained Pro-Pro junctions.

Research Mechanisms

In published in vitro and non-human research, Semax has been characterized as a stabilized analog of the ACTH(4-7) pharmacophore with substantially extended biochemical half-life relative to the unmodified fragment in proteolytic matrices. This profile makes it a useful comparator in pharmacology screens of short stabilized peptides, in receptor-binding methodology research, and in peptide-stability studies of Russian-developed regulatory peptides. ITide Labs supplies Semax as a research-grade reference standard for these applications.

Research Areas

• Peptide-stability and protease-resistance methodology research
• Solid-phase peptide synthesis of short stabilized peptides
• Comparative structure-activity research on ACTH-derived fragments
• Reference standard in analytical method development (HPLC-UV, LC-MS)
• Comparative research on Pro-Gly-Pro-stabilized regulatory peptides

Quality Assurance

ITide Labs releases each lot of Semax against an independent third-party Certificate of Analysis. Lot-specific COAs are published on the corresponding product page once analysis is complete. Identity is confirmed by LC-MS, purity by RP-HPLC-UV, and endotoxin levels by kinetic chromogenic LAL assay. Lyophilized material is stored at 2–8 °C protected from light and is supplied with batch-specific documentation.

Frequently Asked Questions

What is the CAS number for Semax?

The CAS number for Semax is 80714-61-0.

What is the molecular weight of Semax?

The molecular weight of Semax is 813.91 g/mol. The empirical formula is C₃₇H₅₁N₉O₁₀S.

What is the amino acid sequence of Semax?

The single-letter sequence of Semax is MEHFPGP — a 7-residue peptide consisting of Met-Glu-His-Phe (the N-terminal ACTH(4-7) pharmacophore) followed by a C-terminal Pro-Gly-Pro stabilization motif.

How does Semax differ from native ACTH(4-10)?

Semax preserves only the N-terminal four residues of ACTH(4-10) (Met-Glu-His-Phe) and replaces the remaining segment with a Pro-Gly-Pro tripeptide extension. This extension confers resistance to enzymatic cleavage in research matrices.

What is the C-terminal modification on Semax?

Semax carries a C-terminal Pro-Gly-Pro tripeptide extension. The same Pro-Gly-Pro motif is used in the related Russian-developed regulatory peptide Selank.

Why is Semax used in research?

Semax is used as a reference standard in peptide methodology research, in protease-stability assays, in receptor-binding studies on the ACTH(4-10) family, and as a model compound in solid-phase peptide synthesis characterization.

Is Semax a peptide or a small molecule?

Semax is a peptide — a 7-residue synthetic heptapeptide. Its molecular weight (~814 g/mol) places it among the smallest research peptides commonly studied.

What laboratory storage does Semax require?

Lyophilized Semax should be stored at 2–8 °C protected from light for short-term storage and at –20 °C for long-term storage. Reconstituted solutions should be aliquoted and stored frozen.

Who developed Semax?

Semax was developed in the late 1980s by researchers at the Institute of Molecular Genetics in Moscow as part of a structure-activity research program investigating stabilized ACTH-derived peptides.

Is Semax available in different sizes from ITide Labs?

ITide Labs currently supplies Semax as a 10 mg lyophilized lot. Lot-specific Certificates of Analysis are published on the product page once independent third-party characterization is complete.

Citation

ITide Labs. Semax: Chemistry Profile and Research Overview. Las Vegas, NV: ITide Labs LLC; 2026.