N-Acetyl-Semax Amidate [Peptide]

Description

What is N-Acetyl Semax Amidate?

N-Acetyl Semax Amidate is a synthetic heptapeptide structurally derived from the ACTH(4–7) tetrapeptide (Met-Glu-His-Phe), extended at the C-terminus with a Pro-Gly-Pro stabilisation sequence, 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. This core sequence — Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP) — is identical to that of the parent compound Semax. What distinguishes N-Acetyl Semax Amidate from Semax and from its intermediate analogue N-Acetyl Semax are two terminal modifications: acetylation at the N-terminus (Ac-Met) and amidation at the C-terminus (Pro-NH2). The combination of both modifications in a single compound defines the “amidate” designation. Semax was originally developed at the Institute of Molecular Genetics of the Russian Academy of Sciences; N-Acetyl Semax Amidate is a further-modified research analogue developed to investigate the pharmacokinetic consequences of simultaneous N- and C-terminal protection.

The N-terminal acetylation removes the positive charge from the amino terminus, increases resistance to leucine aminopeptidase-mediated hydrolysis, and has been shown to extend peptide stability in plasma and brain tissue preparations relative to unmodified Semax. The C-terminal amidation removes the negative charge from the carboxyl terminus and protects against carboxypeptidase-mediated degradation. Together these modifications are investigated for their capacity to extend effective half-life in biological matrices and improve CNS bioavailability relative to the parent compound in preclinical pharmacokinetic studies. Published direct research on N-Acetyl Semax Amidate specifically is limited; mechanistic interpretation is primarily inferred from the established Semax literature combined with the known pharmacokinetic effects of terminal peptide modifications.

N-Acetyl Semax Amidate is not approved by the Food and Drug Administration for human or veterinary use. 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 Amidate does not share this approval. Research-grade N-Acetyl Semax Amidate from RCDbio is not a pharmaceutical product and is not approved for any use outside laboratory research contexts. 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 Terminally-Modified Heptapeptide (N-Acetylated, C-Amidated ACTH(4-7)/PGP Analogue)
Product Name	N-Acetyl Semax Amidate
Application	Scientific / Research Use Only
CAS Number	2920938-90-3
Molar Mass	854.97 g/mol
Chemical Formula	C39H54N10O10S
PubChem CID	172638603
IUPAC Name	Canonical PubChem IUPAC — N-terminal acetyl, C-terminal amide modifications of the Semax (MEHFPGP) heptapeptide sequence
Amino Acid Sequence	Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH2 (Ac-MEHFPGP-NH2); N-terminal acetylation; C-terminal amidation
Parent Compound	Semax (MEHFPGP; CAS 80714-61-0; MW 813.93 g/mol; C37H51N9O10S) — approved Russia 1996
Intermediate Analogue	N-Acetyl Semax (Ac-MEHFPGP-OH; N-terminal acetylation only; no C-terminal amidation)
Synonyms	NA-Semax Amidate; N-Ac-Semax-NH2; Acetyl-MEHFPGP-amide; NA-Semax-A
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 Amidate 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 prior to use.

How Does N-Acetyl Semax Amidate Work?

Published mechanistic data specific to N-Acetyl Semax Amidate is limited. The following mechanisms are inferred from the established Semax research literature combined with the known effects of N-terminal acetylation and C-terminal amidation on peptide pharmacokinetics in preclinical model systems. This distinction between Semax-derived inference and N-Acetyl Semax Amidate-specific findings is maintained throughout.

N-Terminal Acetylation — Aminopeptidase Resistance Pathway

Acetylation at the N-terminus removes the free amino group’s positive charge and eliminates the substrate recognition site for leucine aminopeptidase, the primary exopeptidase responsible for N-terminal hydrolysis of peptides in plasma and brain tissue. In published Semax analogue stability studies, N-terminal acetylation has been associated with a 30-minute extension of plasma stability relative to unmodified Semax, with additional stability gains reported in brain tissue preparations. This modification has been characterised in peptide pharmacokinetics research as increasing resistance to exopeptidase-mediated degradation without altering the core peptide’s receptor binding geometry in preclinical assay systems.

C-Terminal Amidation — Carboxypeptidase Resistance Pathway

Amidation at the C-terminus replaces the free carboxyl group with an amide group, removing the negative charge at the C-terminus and eliminating the carboxypeptidase substrate recognition site. This structural modification is investigated in preclinical peptide stability research for its capacity to protect the C-terminus from carboxypeptidase B and related enzymes active in plasma and tissue matrices. Combined with N-terminal acetylation, C-terminal amidation provides dual-terminus protection in preclinical models.

BDNF/TrkB Pathway — Inferred from Semax Literature

In rodent hippocampal preparations, Semax exposure has been associated with upregulation of BDNF protein expression and TrkB tyrosine phosphorylation levels. N-Acetyl Semax Amidate is expected to share this pathway interaction based on the preserved core MEHFPGP sequence, with potentially enhanced or prolonged BDNF/TrkB pathway modulation attributable to the extended half-life conferred by dual terminal modification. No directly attributed BDNF/TrkB data for N-Acetyl Semax Amidate specifically is available in the published peer-reviewed literature as of the date of this writing [Dolotov et al., 2006].

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. The preserved MEHFPGP core sequence of N-Acetyl Semax Amidate is expected to retain these receptor interaction properties. The terminal modifications may alter the receptor binding geometry or affinity profile relative to unmodified Semax; this has not been characterised in published peer-reviewed receptor pharmacology studies for N-Acetyl Semax Amidate specifically.

Key Research Findings

In preclinical and in vitro research contexts, Semax and its terminally modified analogues have been associated with the following observations. Unless otherwise noted, findings are derived from Semax research; direct N-Acetyl Semax Amidate data is not available in the peer-reviewed literature.

• Plasma stability enhancement: N-terminal acetylation associated with 30-minute extended plasma stability relative to unmodified Semax in preclinical pharmacokinetic preparations; C-terminal amidation provides additional carboxypeptidase resistance.
• BDNF/TrkB upregulation: Intranasal Semax exposure 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] — data attributed to parent Semax; not yet directly replicated for N-Acetyl Semax Amidate.
• Neuroinflammatory gene suppression: Semax associated with proinflammatory mRNA suppression (Il1a, Il1b, Il6, Ccl3, Cxcl2) in rodent tMCAO ischemia models [Stavchansky et al., 2021] — inferred applicable to N-Acetyl Semax Amidate via conserved core sequence.
• Brain tissue stability: N-terminal acetylation reported in preclinical preparations to increase stability in brain tissue relative to unmodified Semax, suggesting potentially prolonged CNS exposure in experimental systems.
• No direct comparative data: No peer-reviewed study has directly compared N-Acetyl Semax Amidate against Semax or N-Acetyl Semax in matched preclinical biological activity assays as of the date of this writing.

All findings listed above are derived from preclinical or in vitro data. No human clinical trial data has been established for N-Acetyl Semax Amidate. Mechanistic inferences from Semax literature are stated as inferences, not established 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 Amidate?

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

Terminal Modification Pharmacokinetics Studies N-Acetyl Semax Amidate is employed as the primary reference compound for characterising the pharmacokinetic consequences of combined N-terminal acetylation and C-terminal amidation on a defined heptapeptide sequence. In vitro plasma stability assays and brain tissue homogenate preparations compare degradation kinetics of the amidate form against Semax, N-Acetyl Semax, and Semax Amidate to isolate the contributions of each terminal modification.

Comparative ACTH(4-7) Analogue Pharmacology As the most terminally protected member of the Semax analogue family, N-Acetyl Semax Amidate is employed in comparative receptor pharmacology studies examining how N/C-terminal protection alters melanocortin receptor binding profiles, BDNF pathway activation kinetics, and downstream signalling in isolated cell preparations.

BDNF Pathway and Neuroplasticity Research Based on the preserved MEHFPGP core sequence, N-Acetyl Semax Amidate is investigated in preclinical models of hippocampal BDNF expression, TrkB receptor activation, and neuroplasticity markers. Research examines whether enhanced terminal stability produces extended or amplified neurotrophin pathway activation relative to parent Semax in rodent in vivo models.

Cerebral Ischemia-Reperfusion Research In preclinical tMCAO and pMCAO rodent models, N-Acetyl Semax Amidate is investigated for neuroinflammatory gene expression modulation consistent with Semax’s characterised profile, examining whether dual terminal protection enhances or extends the proinflammatory mRNA suppression observed with Semax in ischemia-reperfusion systems.

Peptide Design and SAR Studies N-Acetyl Semax Amidate occupies a defined position in the Semax analogue series — Semax → N-Acetyl Semax → Semax Amidate → N-Acetyl Semax Amidate — making it a useful endpoint compound for SAR investigations examining how terminal modifications progressively alter stability, bioavailability, and receptor interaction profiles within a conserved core sequence.

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

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

• Generally low acute toxicity profile reported for Semax at doses used in neuroprotection research; N-Acetyl Semax Amidate is expected to share this profile based on the preserved core sequence, though this has not been directly characterised
• Methionine residue at position 1 is susceptible to oxidative modification under aerobic storage conditions; this applies to all Semax analogues and may alter activity in experimental systems
• The enhanced plasma stability of N-Acetyl Semax Amidate relative to Semax means its biological effects may persist for longer periods in preclinical in vivo experimental systems — a relevant variable in experimental design
• No human safety or tolerability data has been established for N-Acetyl Semax Amidate. These observations are derived from Semax preclinical literature and should not be extrapolated to N-Acetyl Semax Amidate or to human or animal outcomes.

Risk & Handling

Handling Precautions

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

Exposure Risks

Risk Tier: LOW–MODERATE

N-Acetyl Semax Amidate shares the generally low acute toxicity profile of parent Semax based on structural similarity. Its CNS-active profile — BDNF pathway modulation, melanocortin receptor interactions, potential neuromodulatory activity — 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 has been established for N-Acetyl Semax Amidate.

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 or argon overlay for working solutions requiring extended storage
• Avoid strongly oxidising conditions or prolonged storage at elevated temperatures

Frequently Asked Questions

Q: What is N-Acetyl Semax Amidate and how does it differ from Semax? A: N-Acetyl Semax Amidate is a terminally modified analogue of Semax sharing the same MEHFPGP core heptapeptide sequence. It adds two modifications: N-terminal acetylation (Ac-Met) and C-terminal amidation (Pro-NH2). Semax has a free amino N-terminus and a free carboxyl C-terminus. N-Acetyl Semax sits between them with only N-terminal acetylation. The amidate form carries both modifications simultaneously, providing dual-terminus protection against exopeptidase degradation. It is not approved by the FDA and is intended strictly for laboratory research purposes.

Q: Is N-Acetyl Semax Amidate better studied than Semax? A: No. Semax has a substantially larger body of published peer-reviewed research — including clinical studies in Russia — than N-Acetyl Semax Amidate. Published direct research on N-Acetyl Semax Amidate specifically is limited; the compound’s expected pharmacological properties are primarily inferred from the Semax literature combined with the established chemistry of terminal peptide modifications. Researchers should account for this distinction when interpreting available data.

Q: What does the “amidate” designation mean? A: “Amidate” refers to C-terminal amidation — the replacement of the free carboxyl group at the C-terminus (Pro-OH in Semax) with an amide group (Pro-NH2). This modification removes the negative charge at the C-terminus and eliminates carboxypeptidase substrate recognition. Combined with N-terminal acetylation, it provides dual-terminus protection. The term is used to distinguish this compound from N-Acetyl Semax, which carries only the N-terminal acetylation without C-terminal amidation.

Q: What is the plasma half-life of N-Acetyl Semax Amidate relative to Semax? A: Published pharmacokinetic comparison data is limited. N-terminal acetylation of Semax has been associated with a 30-minute extension of plasma stability relative to unmodified Semax in preclinical stability studies; C-terminal amidation provides additional carboxypeptidase protection. The combined effect on plasma half-life has not been characterised in a standardised preclinical pharmacokinetic study published in peer-reviewed literature as of the date of this writing. These observations are from in vitro stability assay data and should not be extrapolated to human pharmacokinetics.

Q: How should N-Acetyl Semax Amidate be stored? A: Lyophilized N-Acetyl Semax Amidate 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 under aerobic conditions; minimise oxygen exposure. Repeated freeze-thaw cycles are not recommended.

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

Related Research Compounds

Researchers investigating N-Acetyl Semax Amidate 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 for N-Acetyl Semax Amidate research, with the largest published literature base in the Semax analogue family including Russian clinical data.
• N-Acetyl Semax — The N-terminally acetylated form of Semax without C-terminal amidation; the intermediate analogue between Semax and N-Acetyl Semax Amidate for comparative terminal modification pharmacokinetic studies.
• N-Acetyl Selank — A terminally acetylated analogue of the Selank heptapeptide; shares the N-terminal acetylation modification strategy and is commonly investigated alongside N-Acetyl Semax Amidate in comparative neuropeptide stability 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. Medvedeva, E. V., Dmitrieva, V. G., Povarova, O. V., Limborska, S. A., Skvortsova, V. I., Myasoedov, N. F., & Dergunova, L. V. (2014). The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics, 15, 228. https://pubmed.ncbi.nlm.nih.gov/24661604/ 

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

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