N-Acetyl Semax Amidate

01 · What it is

Two papers in PubMed mention an acetylated form of Semax. Neither of them studies the compound sold under this name, and one of them has no abstract.

That is the entire indexed evidence base, and everything else in this guide follows from it.

What the name claims. N-Acetyl Semax Amidate — sold as NA-Semax-Amidate or NASA — is described as Semax with two chemical modifications: an acetyl group on the N-terminus and an amide on the C-terminus. Both are standard peptide-chemistry moves for the same purpose. The free amino group at one end and the free carboxyl at the other are the recognition points for aminopeptidases and carboxypeptidases; capping them is the oldest trick for slowing enzymatic degradation. The claim attached to the product is that this makes it more stable and therefore more potent than Semax.

What the literature contains. A 2013 paper titled “Stability of Semax acetyl to proteolysis in various biological media” ³. PubMed carries no abstract for it, so this guide can report its title and nothing about its methods, its media, its comparator or its result. A 2016 paper examining how N-terminal acetylation of Semax changes the peptide’s coordination of copper(II) and zinc(II) ions, which reports that acetylation modifies Semax’s ability to form complexes with Cu(II) and that the amino-free form produces a redox-stable complex species ⁴.

Neither concerns the amidated form. Both papers address N-terminal acetylation only. The C-terminal amidation that the commercial name specifies does not appear in either. So the two papers that exist are about a molecule that differs from the one sold by one of its two modifications.

And the commercial name has no scientific referent. The exact strings “acetyl semax” and “acetyl selank” are not present in PubMed’s phrase index — the database returns that message directly. The compound is retrievable only as “Ac-Semax” or “Semax acetyl” inside the text of those two papers.

Nothing has been given to an animal, let alone a person. No pharmacology, no behavioural study, no pharmacokinetics, no toxicology, no trial. Whatever is claimed for this compound rests on the parent compound’s literature plus an assumption that two chemical caps improve it.

That assumption is not obviously safe, and Section 3 explains why.

02 · Evidence at a glance

Evidence grade

Preclinical — a floor, not a finding. No study of this compound exists at any level

Claimed structure

Semax with N-terminal acetylation and C-terminal amidation

Parent compound

Semax: Met-Glu-His-Phe-Pro-Gly-Pro, i.e. ACTH(4-7) plus Pro-Gly-Pro ⁵

Indexed papers mentioning an acetylated Semax

2 — and neither concerns the amidated form ^3,4

Abstract availability

None for the stability paper ³

Name in PubMed’s phrase index

Absent

In vitro pharmacology

None

Animal studies

None

Human studies

None

Human subjects to date

0

Pharmacokinetics

None, in any species

What the chemistry papers actually report

Altered Cu(II) and Zn(II) coordination on acetylation ⁴

Approval status

None, any jurisdiction

03 · Mechanism of action

This section describes what the modifications do chemically and what the parent compound is proposed to do. It does not describe what N-Acetyl Semax Amidate does, because nothing is known about that.

What capping the termini achieves

Exopeptidases work from the ends of a peptide inward. Aminopeptidases require a free α-amino group; carboxypeptidases require a free α-carboxyl. Acetylating one end and amidating the other removes both recognition features, which typically extends a short peptide’s survival in plasma and tissue by a substantial factor.

That is well-established chemistry and it is the entire rationale for the compound. The 2013 paper’s title indicates that stability of an acetylated Semax was measured in various biological media ³ — which is exactly the experiment the rationale calls for, and whose result this guide cannot report because the record carries no abstract.

Why more stable is not automatically more active

Two reasons, and the second is specific to this molecule.

First, the general one. A peptide’s termini are frequently part of its pharmacophore. Capping them extends half-life and can simultaneously abolish binding — the trade-off documented for PEGylation in a different family of this project, where the modification “frequently comes at the cost of reduced bioactivity.” Whether Semax’s activity survives acetylation and amidation is an empirical question that the two indexed papers do not answer.

Second, the specific one, and it is the more interesting. The most-cited mechanistic finding for the parent compound is that Semax and Pro-Gly-Pro alone both activate transcription of neurotrophins and their receptor genes after cerebral ischaemia ². Pro-Gly-Pro is Semax’s C-terminal tripeptide. If the free C-terminus of that tripeptide — or its liberation by proteolysis — is part of how the parent works, then amidating the C-terminus does not stabilise the active species. It blocks it.

A modification sold as making the compound work better may, on the parent literature’s own best mechanistic finding, prevent the step that produces the effect. Nobody has tested this either way.

What the metal-binding paper found

N-terminal acetylation modulates Semax’s chemical and biological properties by changing its ability to form complex species with Cu(II); in the amino-free form the resulting complex is redox-stable ⁴.

This is a real result about the acetylated molecule and it is a coordination chemistry result. It establishes that acetylation changes the molecule’s behaviour — which cuts against the assumption that capping is pharmacologically neutral — without establishing what that change does in a cell.

The parent’s own mechanism is unresolved

Semax has no identified receptor. Its developers’ own account attributes activity to the combined action of the peptide and its degradation products [see the Semax guide]. A compound built to prevent degradation of a parent whose proposed mechanism involves its degradation products is a compound whose rationale is in tension with the literature it derives from.

04 · Key research findings

There are no research findings for N-Acetyl Semax Amidate. What follows is what the adjacent literature establishes, labelled for what it is.

On acetylated Semax, in chemistry. N-terminal acetylation modifies Semax’s coordination of copper(II) and zinc(II) and its associated biological properties, with the amino-free form yielding a redox-stable complex ⁴.

The only substantive published result on any modified Semax. It is inorganic chemistry, and it says the modification is not inert.

On acetylated Semax, in stability. A 2013 report examined stability of Semax acetyl to proteolysis in various biological media ³. No abstract is indexed.

This guide cites it as a title. Whether the acetylated form was more stable, how much more, in which media, and against what comparator are all unreported in the retrievable record.

On the parent, for context only. Semax has been given to patients in Russian-language studies — 30 patients in acute hemispheric ischaemic stroke ¹ among them — and to healthy volunteers in placebo-controlled resting-state fMRI showing changes in brain connectivity within 20 minutes of intranasal dosing ⁶, with a larger connectomic study in 52 participants ⁷. Its structure is correctly ACTH(4-7) plus Pro-Gly-Pro rather than ACTH(4-10) ⁵. Both Semax and Pro-Gly-Pro activate neurotrophin gene transcription after cerebral ischaemia ².

None of this is evidence about the acetylated-amidated compound. It is included so that a reader can see exactly what is being borrowed when the parent’s results are cited for the derivative.

Contemporary mentions. Reviews list Semax among neuroactive peptides of interest ^8,9. Neither names the acetylated or amidated forms.

05 · Evidence overview

06 · Safety profile

Animal data. None. No study of N-Acetyl Semax Amidate in any species exists.

Human data. None. There is no reported human exposure to this compound in the peer-reviewed literature at any dose, by any route, for any duration.

What is genuinely unknown. Everything specific to the compound, and four things worth naming. Whether it retains any of the parent’s activity, given that acetylation demonstrably alters the molecule’s chemistry ⁴ and amidation blocks the C-terminus implicated in the parent’s best mechanistic finding ². Its half-life, which is the whole reason it exists and which no retrievable paper reports for the acetylated form and no paper at all reports for the amidated form. What a longer-lived version of a compound with no identified receptor does — extending exposure to an agent whose target is unknown extends exposure to unknown off-target effects along with the intended ones. And the endocrine question inherited from the parent: this is a fragment derived from a pituitary hormone, no study has measured HPA axis function after administration of Semax, and a protease-resistant version would sustain any such effect for longer.

The absence of adverse-event reports for this compound is not reassurance. There are no reports because there are no studies.

07 · US regulatory status

Current as of 6 September 2026. N-Acetyl Semax Amidate is not approved as a drug in the United States or any other jurisdiction and is not a controlled substance.

The parent compound is registered in Russia for stroke indications; this guide does not characterise the terms of that registration, and in any case a registration covering Semax does not extend to a chemically modified derivative. No marketing authorisation, investigational programme or regulatory review of the acetylated-amidated form appears anywhere in the peer-reviewed record.

Under the World Anti-Doping Code, substances not approved for human therapeutic use by any governmental regulatory health authority fall within class S0. Competitors should consult the current Prohibited List directly rather than rely on secondary summaries, including this one.

08 · Limitations of the evidence

1. No study of this compound exists. Not thin evidence — none. The two papers that mention an acetylated Semax ^3,4 are chemistry papers, and neither addresses the amidated form named on the product.
2. One of those two papers has no abstract. The stability study ³ is retrievable as a title, an author list and a journal citation. Its result — the single most relevant fact anyone could want about this compound’s rationale — is not in the indexed record.
3. The Preclinical grade is a floor, not a finding. The rubric’s lowest tier describes in vitro and animal data. This compound has neither. It receives the lowest available grade because there is nowhere lower, exactly as for PEG-MGF.
4. The commercial name has no scientific referent. “Acetyl semax” is not in PubMed’s phrase index. No published characterisation exists under the name on the label.
5. The stability rationale may work against the parent’s proposed mechanism. Pro-Gly-Pro alone reproduces the parent’s neurotrophin effect ²; amidating the C-terminus caps that tripeptide’s free end. Whether this matters is untested, and it is a reason to expect the modification could reduce activity rather than increase it.
6. Acetylation is demonstrably not inert. It changes Cu(II) and Zn(II) coordination and the associated biological properties ⁴. A modification presented as merely protective has documented chemical consequences.
7. Everything claimed for this compound is borrowed from the parent, whose own human evidence is Russian-language and unread by this guide ¹, whose best-controlled human data are imaging studies in healthy volunteers ^6,7, and which has no identified receptor.
8. No study has compared the modified and unmodified compounds in any biological assay. Even the most basic claim — that the derivative is more potent — has never been tested against Semax.
9. Nothing is known about commercial material. No published analysis has examined the identity, purity or actual modification state of any product sold under this name, and a purchaser has no reference standard to compare against.

09 · References

1. Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat’ko VN, Zhuravleva EIu, Vanichkin AV. [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26–34. Clinical trial. Russian.

   PMID 11517472 ↗

2. Dmitrieva VG, Povarova OV, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol. 2010 Jan;30(1):71–79.

   PMID 19633950 ↗

3. Shevchenko KV, Nagaev IY, Andreeva LA, Shevchenko VP, Myasoedov NF. Stability of Semax acetyl to proteolysis in various biological media. Dokl Biol Sci. 2013 Mar;449:110–112. No abstract available.

   PMID 23652441 ↗

4. Magrì A, Tabbì G, Giuffrida A, Pappalardo G, Satriano C, Naletova I, Nicoletti VG, Attanasio F. Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties. J Inorg Biochem. 2016 Nov;164:59–69.

   PMID 27586814 ↗

5. Medvedeva EV, Dmitrieva VG, Limborska SA, Myasoedov NF, Dergunova LV. Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats. Mol Genet Genomics. 2017 Jun;292(3):635–653.

   PMID 28255762 ↗

6. Lebedeva IS, Panikratova YR, Sokolov OY, Kupriyanov DA, Rumshiskaya AD, Kost NV, Myasoedov NF. Effects of Semax on the default mode network of the brain. Bull Exp Biol Med. 2018 Sep;165(5):653–656.

   PMID 30225715 ↗

7. Panikratova YR, Lebedeva IS, Sokolov OY, Rumshiskaya AD, Kupriyanov DA, Kost NV, Myasoedov NF. Functional connectomic approach to studying Selank and Semax effects. Dokl Biol Sci. 2020 Jan;490(1):9–11.

   PMID 32342318 ↗

8. Rahman OF, Lee SJ, Seeds WA. Therapeutic peptides in orthopaedics: applications, challenges, and future directions. J Am Acad Orthop Surg Glob Res Rev. 2026 Jan 2;10(1):e25.00236.

   PMID 41490200 ↗

9. Mavrych V, Shypilova I, Bolgova O. Therapeutic peptides in gerontology: mechanisms and applications for healthy aging. Front Aging. 2026 Apr 7;7:1790247.

   PMID 42021992 ↗