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PeptideHormone

Semax

A Russian ACTH(4-10)-derived nootropic that acts through neurotrophins, not the adrenal axis.

Research peptideLimitedUnapproved

A piece of a peptide can come to mean something its parent never did, and act on a system the parent never touched.

Identity

Class
Synthetic heptapeptide — ACTH(4-7) extended with Pro-Gly-Pro
Source
Synthetic; based on the melanocortin fragment ACTH(4-10)
Receptor
No classical melanocortin-receptor role; drives BDNF/neurotrophin signaling centrally

Key properties

Evidence floorPreclinicalREF1PRE1
Molecular weight
~813.9 Da
REF
Half-life (native)
Minutes in plasma (CNS effects outlast)
PRE

Approximate values for the native hormone; engineered analogs are often deliberately larger and far longer-acting. Each figure carries its own provenance tier, and the floor is the weakest of them - the Standard.

Mechanism

Semax is an engineered fragment of ACTH(4-10) — the melanocortin sequence stripped of its cortisol-releasing hormone activity and capped with a C-terminal Pro-Gly-Pro that resists peptidase cleavage. Rather than acting as a melanocortin hormone, it upregulates BDNF and its receptor TrkB and shifts dopaminergic and serotonergic tone, the basis of the nootropic and neuroprotective effects studied largely in Russian programs, where it is a registered drug.

Reference notes

  • It keeps the neuroactive core of ACTH(4-10) while shedding the steroidogenic hormone activity — a fragment repurposed away from its parent's endocrine role.
  • Its central effects run through BDNF/TrkB and monoamine systems, not the melanocortin receptors.
  • Registered and used clinically in Russia; independent Western trial evidence remains limited.

Regulatory status

United States · reviewed September 2026
UnapprovedSemax is sold outside the approved-drug system as research-use-only material, with no FDA approval for human use.
Basis
Approved as a nootropic in Russia; no FDA approval or US trials. In July 2026 the Pharmacy Compounding Advisory Committee voted 8–5 with one abstention to recommend adding it to the 503A list, against FDA staff advice; the vote is non-binding and the status stands pending rulemaking.

Status describes the molecule as a drug substance under US law and is an editorial reading of the public record — approvals, trial registrations, and the FDA 503A bulk-substances list. It is not legal advice and it changes; the review date above is the last time the table was checked. Other jurisdictions are noted only where they differ materially.

Common questions

What is Semax?
A Russian ACTH(4-10)-derived nootropic that acts through neurotrophins, not the adrenal axis. Structurally it is Synthetic heptapeptide — ACTH(4-7) extended with Pro-Gly-Pro.
How does Semax work?
Semax is an engineered fragment of ACTH(4-10) — the melanocortin sequence stripped of its cortisol-releasing hormone activity and capped with a C-terminal Pro-Gly-Pro that resists peptidase cleavage. Rather than acting as a melanocortin hormone, it upregulates BDNF and its receptor TrkB and shifts dopaminergic and serotonergic tone, the basis of the nootropic and neuroprotective effects studied largely in Russian programs, where it is a registered drug.
How strong is the evidence for Semax?
PeptideHormone grades Semax at the "Limited" evidence tier — the evidence is sparse, older, or mostly community-reported. It is catalogued as a community research peptide outside the approved-drug system, and the tier is an editorial judgment about the public literature that can change as the science does.
What is the half-life of Semax?
The reported circulating half-life of Semax is Minutes in plasma (CNS effects outlast).
Is Semax FDA-approved?
No — as of September 2026, Semax is sold outside the approved-drug system as research-use-only material, with no FDA approval for human use. Approved as a nootropic in Russia; no FDA approval or US trials. In July 2026 the Pharmacy Compounding Advisory Committee voted 8–5 with one abstention to recommend adding it to the 503A list, against FDA staff advice; the vote is non-binding and the status stands pending rulemaking. Status is US-centric and can change; check the FDA record for the current position.

In the literature

Live registry counts · retrieved

Searched as Semax. Counts are search hits from the primary registries, not a curated set and not a grade – a measure of how much work exists on Semax, not how it turned out.

Selected literature

Curated peer-reviewed reviews, sourced from PubMed. Selected for relevance, not exhaustive — open any entry on PubMed for the full record and its primary citations.

  1. 1.Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents · Neurochemical research, 2005 · PMID 16362768
  2. 2.Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia · Cellular and molecular neurobiology, 2010 · PMID 19633950
  3. 3.Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats · Neuropeptides, 2021 · PMID 33418449

External references

Semax in the public knowledge graph — the same entity resolved across the authoritative chemistry and protein databases.