N-Acetyl Semax [Peptide]

Description

What is N-Acetyl Semax?

N-Acetyl Semax is a synthetic heptapeptide analogue of Semax (MEHFPGP) carrying an N-terminal acetyl modification — making it the intermediate compound in the Semax analogue family between the parent compound Semax (H-MEHFPGP-OH) and N-Acetyl Semax Amidate (Ac-MEHFPGP-NH2). Its core sequence is Met-Glu-His-Phe-Pro-Gly-Pro, structurally based on the ACTH(4–7) tetrapeptide (Met-Glu-His-Phe) with a C-terminal Pro-Gly-Pro stabilisation extension — making it an analogue of ACTH(4–10) in which the native Arg-Trp-Gly residues at positions 8–10 are replaced by Pro-Gly-Pro to enhance metabolic stability while eliminating steroidogenic activity. The acetyl group at the N-terminus removes the free amino group’s positive charge and eliminates the leucine aminopeptidase recognition site, extending resistance to N-terminal exopeptidase degradation relative to unmodified Semax in plasma and brain tissue preparations.

An important nomenclature note: in commercial research peptide supply, “N-Acetyl Semax” and “N-Acetyl Semax Amidate” are frequently used interchangeably. CAS 2920938-90-3 is assigned in most databases to the doubly-modified form (Ac-MEHFPGP-NH2) with both N-terminal acetylation and C-terminal amidation. A true N-Acetyl Semax with a free C-terminal carboxyl (Ac-MEHFPGP-OH) — the singly-modified form — does not have a separately widely-published CAS registry number in the peer-reviewed or commercial literature. Researchers should verify from the product’s analytical documentation (COA/HPLC data) which terminal configuration is supplied, as the free acid and amidated forms differ in MW by approximately one unit and carry different carboxypeptidase resistance profiles.

Semax, the parent compound, has been approved as a registered pharmaceutical in Russia since 1996 for clinical indications including post-stroke recovery, optic nerve atrophy, and cognitive impairment. N-Acetyl Semax does not share this approval. Research-grade N-Acetyl Semax from RCDbio is not a pharmaceutical product and is not approved for any use outside laboratory research contexts. It is not approved by the Food and Drug Administration for human or veterinary use. It is not a dietary supplement and is not intended for human consumption or therapeutic self-administration. All RCDbio research compounds are supplied strictly for laboratory and research purposes only.

Chemical Properties

Property	Detail
Product Type	Synthetic N-Terminally Acetylated Heptapeptide (ACTH(4-7)/PGP Analogue)
Product Name	N-Acetyl Semax
Application	Scientific / Research Use Only
CAS Number	2920938-90-3 (assigned in most databases; note: this CAS is also used for the doubly-modified N-Acetyl Semax Amidate form — verify from COA which terminal configuration is supplied)
Molar Mass	~855.97 g/mol (Ac-MEHFPGP-OH, free acid C-terminus); 854.97 g/mol (Ac-MEHFPGP-NH2, amidated C-terminus) — verify from product COA
Chemical Formula	C39H53N9O11S (free acid C-terminus); C39H54N10O10S (amidated C-terminus)
PubChem CID	172638603 (indexed as N-Acetyl Semax Amidate, Ac-MEHFPGP-NH2, under the “N-acetyl semax” synonym)
IUPAC Name (Amidate form)	N-acetyl-L-methionyl-L-alpha-glutamyl-L-histidyl-L-phenylalanyl-L-prolyl-glycyl-L-prolinamide
Amino Acid Sequence	Ac-Met-Glu-His-Phe-Pro-Gly-Pro (Ac-MEHFPGP); N-terminal acetylation; C-terminus free acid (OH) or amidated (NH2) depending on form supplied
Parent Compound	Semax (H-MEHFPGP-OH; CAS 80714-61-0; MW 813.93 g/mol; C37H51N9O10S) — approved Russia 1996
Semax Analogue Family	Semax (no modification) → N-Acetyl Semax (N-terminal acetyl only) → Semax Amidate (C-terminal amide only) → N-Acetyl Semax Amidate (both modifications)
Synonyms	NA-Semax; Acetyl-Semax; N-Ac-Semax; Ac-MEHFPGP; N-Acetyl Semax Acetate
Physical Form	Lyophilized white to off-white powder
Solubility	Soluble in sterile water and PBS; compatible with standard aqueous buffers
Storage (Lyophilized)	−20°C; sealed container; protected from light and moisture
Storage (Reconstituted)	4°C; use within 48–72 hours; avoid repeated freeze-thaw cycles
Purity	≥98% (HPLC verified, independent third-party laboratory analysis)
WADA Status	N-Acetyl Semax is not explicitly named on the 2026 WADA Prohibited List. As a non-approved synthetic CNS-active peptide analogue, S0 (Non-Approved Substances) provisions may apply in sport-adjacent research contexts. Verify at GlobalDRO.com before use.

How Does N-Acetyl Semax Work?

Published mechanistic data specific to N-Acetyl Semax are limited. The mechanisms below are derived from the established Semax research literature and the known pharmacokinetic effects of N-terminal acetylation. This distinction is maintained throughout.

N-Terminal Acetylation — Aminopeptidase Resistance

Acetylation at the N-terminus removes the free amino group and eliminates the leucine aminopeptidase recognition site — the primary exopeptidase responsible for N-terminal hydrolysis of Semax in plasma and brain tissue. In Semax analogue stability studies, N-terminal acetylation is associated with extended plasma stability relative to unmodified Semax. This modification does not alter the core heptapeptide sequence and is not expected to change receptor binding geometry in preclinical assay systems. The C-terminus, if free acid (OH), remains susceptible to carboxypeptidase degradation — distinguishing N-Acetyl Semax from N-Acetyl Semax Amidate, which carries additional C-terminal amide protection.

BDNF/TrkB Pathway Modulation — Inferred from Semax Literature

In rodent hippocampal preparations, Semax exposure has been associated with upregulation of BDNF protein expression and TrkB tyrosine phosphorylation. N-Acetyl Semax is expected to share this pathway interaction through the preserved MEHFPGP core sequence. Potentially enhanced or prolonged BDNF/TrkB pathway modulation is hypothesised from the extended plasma stability conferred by N-terminal acetylation. No directly attributed BDNF/TrkB data for N-Acetyl Semax specifically is available in the published peer-reviewed literature [Dolotov et al., 2006].

Neuroinflammatory Gene Expression Modulation — Inferred from Semax Literature

In rodent tMCAO ischaemia-reperfusion models, Semax has been associated with suppression of proinflammatory cytokine mRNA transcripts (Il1a, Il1b, Il6, Ccl3, Cxcl2) and protein-level modulation of CREB, MMP-9, c-Fos, and JNK in cortical and subcortical tissue preparations [Filippenkov et al., 2021; Stavchansky et al., 2021]. N-Acetyl Semax is expected to share this profile through the preserved core sequence, with potentially extended activity duration relative to parent Semax at equivalent doses.

Melanocortin Receptor Interactions — Inferred from Semax Literature

Semax has been investigated for interactions with melanocortin receptor subtypes, particularly MC4 and MC5, in isolated cell preparations, with incomplete characterisation of its binding mode (agonism, partial agonism, or antagonism) across experimental systems. N-Acetyl Semax’s preserved MEHFPGP core is expected to retain these receptor interaction properties; terminal acetylation may modify the binding geometry or affinity profile, but this has not been characterised in published studies for N-Acetyl Semax specifically.

Key Research Findings

In preclinical and in vitro research contexts, Semax and its acetylated analogues have been associated with the following observations. Unless otherwise noted, findings are from Semax research; no direct N-Acetyl Semax-specific PubMed data is available in the published literature.

• Plasma stability: N-terminal acetylation is associated with extended plasma stability relative to unmodified Semax in preclinical pharmacokinetic preparations; the aminopeptidase substrate recognition site is eliminated.
• BDNF/TrkB upregulation: Intranasal Semax in rat hippocampal preparations associated with up to 1.4-fold increase in BDNF protein and 1.6-fold increase in TrkB tyrosine phosphorylation [Dolotov et al., 2006] — attributed to parent Semax; not directly replicated for N-Acetyl Semax.
• Proinflammatory mRNA suppression: Semax is associated with Il1a, Il1b, Il6, Ccl3, and Cxcl2 mRNA suppression in rodent tMCAO ischaemia models [Stavchansky et al., 2021].
• Brain protein expression: Semax is associated with CREB upregulation and MMP-9/c-Fos/JNK downregulation in ischaemia-reperfusion rodent cortical preparations [Filippenkov et al., 2021].
• Dopaminergic/serotonergic modulation: Semax activates dopaminergic and serotonergic brain systems in rodent preparations [Eremin et al., 2005] — inferred applicable to N-Acetyl Semax via preserved core sequence.

All findings listed above are derived from preclinical or in vitro data. No human clinical trial data have been established for N-Acetyl Semax. Mechanistic inferences from Semax literature are stated as inferences, not facts, for this compound. These observations do not constitute evidence of efficacy or safety in any human condition or organism.

What are the Potential Research Applications of N-Acetyl Semax?

In controlled laboratory environments, N-Acetyl Semax has been investigated for the following research applications. These are observed in preclinical and in vitro contexts and do not constitute claims of efficacy or safety in any organism.

N-Terminal Modification and Plasma Stability Studies N-Acetyl Semax is employed as the singly-modified reference compound in studies characterising the pharmacokinetic effect of N-terminal acetylation on Semax-class heptapeptides. Comparative in vitro plasma stability assays examine the degradation kinetics of N-Acetyl Semax versus unmodified Semax and versus the doubly-modified N-Acetyl Semax Amidate, isolating the contribution of N-terminal protection alone.

BDNF Pathway and Neuroplasticity Research Based on the preserved MEHFPGP core, N-Acetyl Semax is investigated in preclinical hippocampal BDNF expression and TrkB activation models. Research examines whether N-terminal acetylation-mediated extended stability produces quantifiably different BDNF/TrkB modulation profiles compared to parent Semax at equivalent molar doses in rodent in vivo and isolated cell preparations.

Comparative ACTH(4-7) Analogue SAR Studies N-Acetyl Semax occupies a defined intermediate position in the Semax analogue series (Semax → N-Acetyl Semax → Semax Amidate → N-Acetyl Semax Amidate), making it a key reference compound for SAR investigations characterising how progressive terminal modification alters stability, receptor interaction profiles, and downstream pathway activity across the series.

Cerebral Ischaemia-Reperfusion and Neuroinflammatory Research. In rodent tMCAO and pMCAO model systems, N-Acetyl Semax is investigated for neuroinflammatory gene expression modulation, proinflammatory cytokine suppression, and neuroprotective protein expression changes consistent with the characterised Semax profile, examining whether acetylation-enhanced stability modifies these responses.

Melanocortin Receptor Pharmacology As a Semax structural analogue, N-Acetyl Semax is employed in receptor competition and binding assays examining MC4 and MC5 receptor interaction profiles. Research aims to characterise whether N-terminal acetylation alters the binding mode, affinity, or selectivity profile at melanocortin receptor subtypes relative to unmodified Semax.

What are the Potential Side Effects of N-Acetyl Semax?

The following observations are inferred from Semax preclinical literature; direct side effect data for N-Acetyl Semax are not available in the peer-reviewed literature.

• Generally low acute toxicity profile reported for Semax at research-relevant doses in rodent preclinical studies; N-Acetyl Semax is expected to share this profile through the preserved core sequence
• Methionine residue at position 1 is susceptible to oxidative modification under aerobic storage conditions — applicable to all Semax analogues carrying the intact Met residue
• Enhanced plasma stability relative to Semax means biological effects in preclinical in vivo systems may persist for a longer duration — a relevant experimental design variable
• No human safety or tolerability data have been established for N-Acetyl Semax. These observations are inferred from Semax preclinical literature and should not be extrapolated to N-Acetyl Semax or to human or animal outcomes.

Risk & Handling

Handling Precautions

N-Acetyl Semax should only be handled by trained laboratory personnel. Appropriate PPE is required: nitrile gloves, a laboratory coat, and eye protection at a minimum. When working with lyophilized powder, use within a laminar flow cabinet or a clean area. Avoid aerosol generation during reconstitution. The methionine residue is susceptible to oxidative modification — minimise exposure to atmospheric oxygen and light.

Exposure Risks

Risk Tier: LOW–MODERATE

N-Acetyl Semax shares the generally low acute toxicity profile of parent Semax. Its CNS-active profile — BDNF pathway modulation, melanocortin receptor interactions, monoaminergic system effects — means accidental systemic exposure may produce pharmacological effects at CNS-expressing targets. Enhanced terminal stability relative to Semax means effects may be more persistent in the event of inadvertent exposure. No human safety or tolerability data have been established for N-Acetyl Semax.

Storage

• Lyophilized form: Store at −20°C in original sealed, light-protected container with desiccant
• Reconstituted form: Store at 4°C; use within 48–72 hours of reconstitution
• Do not subject to repeated freeze-thaw cycles; Met1 oxidative modification risk increases with each cycle
• Protect from light and atmospheric oxygen; consider nitrogen overlay for working solutions requiring extended storage

Frequently Asked Questions

Q: What is N-Acetyl Semax, and how does it differ from Semax? A: N-Acetyl Semax shares the MEHFPGP heptapeptide core of Semax but adds N-terminal acetylation, which removes the leucine aminopeptidase cleavage site and extends plasma stability. Unlike N-Acetyl Semax Amidate, N-Acetyl Semax carries only the N-terminal modification without C-terminal amidation. It is not approved by the FDA and is intended strictly for laboratory research purposes.

Q: What is the difference between N-Acetyl Semax and N-Acetyl Semax Amidate? A: N-Acetyl Semax has N-terminal acetylation only (Ac-MEHFPGP-OH; free carboxyl C-terminus). N-Acetyl Semax Amidate has both N-terminal acetylation and C-terminal amidation (Ac-MEHFPGP-NH2), providing dual-terminus protection against both aminopeptidase and carboxypeptidase degradation. The amidate form provides additional C-terminal protection but differs in charge profile at the C-terminus. Researchers should verify from the product’s COA which form is supplied, as “N-Acetyl Semax” and “N-Acetyl Semax Amidate” are sometimes used interchangeably in commercial research peptide supply.

Q: Is there published research specifically on N-Acetyl Semax? A: Published peer-reviewed research specifically characterising N-Acetyl Semax (versus N-Acetyl Semax Amidate or parent Semax) in controlled biological assays is limited. The compound’s expected pharmacological properties are primarily inferred from the Semax research literature combined with established peptide modification chemistry. Most Semax family clinical and preclinical research pertains to the parent compound, which has been approved as a pharmaceutical in Russia since 1996.

Q: What is the plasma half-life of N-Acetyl Semax? A: Published pharmacokinetic half-life data specifically for N-Acetyl Semax in standardised preclinical plasma assays is not available in the published literature. N-terminal acetylation of Semax has been associated with extended plasma stability relative to unmodified Semax in preclinical stability studies; the free C-terminus (if present) remains susceptible to carboxypeptidase degradation compared to the fully amidated form. These observations are from in vitro stability data.

Q: How should N-Acetyl Semax be stored? A: Lyophilized N-Acetyl Semax should be stored at −20°C in a sealed, light-protected container with desiccant. Once reconstituted, store at 4°C and use within 48–72 hours. The methionine residue at position 1 is susceptible to oxidative modification — minimise oxygen exposure and repeated freeze-thaw cycling. Verify the terminal configuration from the product COA before use in stability-sensitive experimental systems.

Q: What toxicity observations have been reported for N-Acetyl Semax? A: No dedicated toxicity studies for N-Acetyl Semax have been published in the peer-reviewed literature. Parent compound Semax has demonstrated a generally low acute toxicity profile in rodent preclinical studies at research-relevant doses; N-Acetyl Semax is expected to share this profile. No human safety or tolerability data have been established. These observations should not be extrapolated to human or animal outcomes.

Related Research Compounds

Researchers investigating N-Acetyl Semax may also be interested in the following compounds currently available for laboratory research at RCDbio:

• Semax — The parent ACTH(4-7)/PGP analogue heptapeptide; the primary reference compound with the largest published literature base, including Russian clinical data and the foundational BDNF/TrkB and neuroinflammatory mechanism data.
• N-Acetyl Semax Amidate — The doubly-modified form with both N-terminal acetylation and C-terminal amidation; the fully-protected Semax analogue for comparative pharmacokinetic studies on dual terminal protection.
• N-Acetyl Selank — The N-terminally acetylated analogue of Selank; shares the N-terminal acetylation modification strategy and is commonly investigated alongside N-Acetyl Semax in comparative neuropeptide stability and CNS pharmacology research.

All products listed are for laboratory and research purposes only.

References

1. Dolotov, O. V., Karpenko, E. A., Inozemtseva, L. S., Seredenina, T. S., Levitskaya, N. G., Rozyczka, J., Dubynina, E. V., Novosadova, E. V., Andreeva, L. A., Alfeeva, L. Y., Kamensky, A. A., Grivennikov, I. A., Myasoedov, N. F., & Engele, J. (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research, 1117(1), 54–60. https://pubmed.ncbi.nlm.nih.gov/16996037/

2. Stavchansky, V. V., Denisova, A. E., Filippenkov, I. B., Sudarkina, O. Y., Gubsky, L. V., Myasoedov, N. F., Limborska, S. A., & Dergunova, L. V. (2021). The Peptide Drug ACTH(4-7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain. Genes, 12(6), 867. https://pubmed.ncbi.nlm.nih.gov/34097675/

3. Filippenkov, I. B., Stavchansky, V. V., Denisova, A. E., Yuzhakov, V. V., Sevan’kaeva, L. E., Sudarkina, O. Y., Dmitrieva, V. G., Gubsky, L. V., Myasoedov, N. F., Limborska, S. A., & Dergunova, L. V. (2021). Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion. International Journal of Molecular Sciences, 22(12), 6179. https://pubmed.ncbi.nlm.nih.gov/34201112/

4. Eremin, K. O., Kudrin, V. S., Saransaari, P., Oja, S. S., Grivennikov, I. A., Myasoedov, N. F., & Rayevsky, K. S. (2005). Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochemical Research, 30(12), 1493–1500. https://pubmed.ncbi.nlm.nih.gov/16362768/ 

Disclaimer

N-Acetyl Semax is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition.

The Food and Drug Administration has not evaluated the statements on our website. This product is not approved for human or veterinary use. Researchers must comply with all applicable local, state, and federal laws and regulations governing the purchase and use of research compounds. By purchasing, you agree to our Terms and Conditions. RCDbio reserves the right to refuse sales to unauthorized individuals.

ATTENTION: All RCDbio products are strictly for LABORATORY AND RESEARCH PURPOSES ONLY. They are not intended for human consumption, veterinary use, or any other non-research application. For queries, complaints, or support, contact support@rcdbio.co