Semax Research Overview
Semax Research Overview
Research-Only Notice & Compliance Boundary
This document is compiled strictly for educational and analytical reference purposes within laboratory, academic, and clinical research settings. The compounds discussed herein are supplied strictly as Research Use Only (RUO) chemicals and are not intended for human or veterinary consumption, diagnostic use, or therapeutic administration. Core Research does not provide dosing, reconstitution, or clinical administration guidelines.
Scientific Context and Research Background of Semax
Semax, the synthetic heptapeptide analogue of adrenocorticotropic hormone (ACTH), occupies a uniquely compelling position within the contemporary landscape of neuropeptide research — one that has drawn sustained academic interest across neuroscience, molecular pharmacology, and translational biology for over three decades.
At our neuro-chemistry research support desk, the enquiries we receive about Semax are rarely superficial. Academic investigators arrive with nuanced questions — about its melanocortin receptor binding profile, about the structural rationale behind its C-terminal Pro-Gly-Pro (PGP) extension, about how its behaviour in solution compares to its parent ACTH(4–7) fragment. These are the questions that reveal a compound with genuine scientific depth, and they are precisely the questions this overview is designed to address with rigour and precision.
Semax was originally developed at the Institute of Molecular Genetics of the Russian Academy of Sciences during the late 1980s and early 1990s, emerging from a systematic programme of ACTH fragment modification aimed at isolating and amplifying the nootropic and neuroprotective properties of the parent hormone whilst eliminating its steroidogenic activity. The resulting compound — Met-Glu-His-Phe-Pro-Gly-Pro, or MEHFPGP — represents a landmark in rational peptide design: a molecule engineered not merely to mimic a biological signal, but to refine and stabilise it.
Within the research peptides landscape in the UK and internationally, Semax is categorised as a melanocortin-system modulator with documented interactions at MC4R and MC5R subtypes, alongside well-characterised effects on brain-derived neurotrophic factor (BDNF) expression, serotonergic and dopaminergic neurotransmission, and neuroinflammatory signalling cascades. Its research significance is therefore multidimensional: it serves simultaneously as a pharmacological probe for melanocortin receptor biology, a model compound for studying neuropeptide stability engineering, and a reference entity in the growing field of cognitive neuroscience research tools.
For research institutions seeking a well-characterised, analytically documented neuropeptide analogue with a substantial published evidence base, Semax represents one of the most thoroughly studied synthetic peptides available within the RUO category. Its identity is unambiguous, its physicochemical properties are well-defined, and its pre-clinical research literature — spanning in vitro receptor binding assays, rodent behavioural models, and gene expression studies — provides a robust scientific framework for continued investigation.
Research Context Note: Semax (ID: O034) is catalogued within the Core Research compounds library under the peptide analogues classification, supplied as a lyophilised powder with full Certificate of Analysis (CoA) documentation. All identity and purity data are generated via HPLC and mass spectrometry prior to release.
Molecular Structure and Physicochemical Properties
Semax is formally designated as the heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro, representing a C-terminally extended analogue of the ACTH(4–7) core sequence (Met-Glu-His-Phe). Its molecular formula is C37H51N9O10S, and its molecular weight is 887.93 g/mol (monoisotopic mass: 887.34 Da). The compound is assigned CAS number 80714-61-0 and is recognised under the INN-adjacent designation Semax, though it does not hold formal INN status given its research-only classification.
The primary sequence — Met¹-Glu²-His³-Phe⁴-Pro⁵-Gly⁶-Pro⁷ — encodes a precise set of physicochemical properties that distinguish Semax from both its parent fragment and other melanocortin-derived research peptides. The N-terminal methionine residue contributes a thioether side chain that participates in the compound’s redox chemistry, rendering it susceptible to oxidation at the sulphur atom under conditions of elevated metal ion concentration or peroxide exposure — a critical consideration for storage and reconstitution protocols. The glutamic acid at position 2 introduces a free carboxylate side chain that contributes to the molecule’s net negative charge at physiological pH, influencing its solubility profile and membrane interaction characteristics.
The histidine residue at position 3 is of particular structural significance. With a pKa of approximately 6.0 for its imidazole side chain, histidine acts as a pH-sensitive charge carrier, transitioning between protonated (positively charged) and neutral states across the physiologically relevant pH range of 6.0–8.0. This property has implications for the compound’s receptor binding geometry, as the imidazole ring is believed to participate in key hydrogen-bonding interactions within the melanocortin receptor binding pocket. The phenylalanine at position 4 — conserved from the parent ACTH(4–7) sequence — contributes an aromatic side chain that is considered essential for melanocortin receptor recognition, consistent with the well-established pharmacophore model for this receptor family.
The C-terminal Pro-Gly-Pro tripeptide extension is the defining structural innovation of Semax relative to its parent fragment. Proline residues at positions 5 and 7 introduce conformational rigidity through their cyclic pyrrolidine ring systems, restricting backbone dihedral angles and imposing a defined secondary structure upon the C-terminal region of the molecule. The intervening glycine at position 6 — the smallest amino acid, devoid of a side chain — provides a flexible hinge between the two proline residues, permitting a degree of conformational adaptability whilst preserving the overall structural constraint imposed by the flanking prolines. This PGP motif is understood to confer resistance to enzymatic degradation by prolyl endopeptidases and other peptidases that would otherwise rapidly cleave the shorter ACTH(4–7) parent sequence in biological matrices.
In terms of physical appearance, Semax is supplied as a white to off-white lyophilised powder. Its solubility profile is characterised by good aqueous solubility, with the compound dissolving readily in water and phosphate-buffered saline (PBS) at concentrations relevant to in vitro research applications. The isoelectric point (pI) is calculated at approximately 4.2, reflecting the net anionic character of the molecule at neutral pH. Log P values estimated by computational methods suggest moderate hydrophilicity, consistent with the compound’s demonstrated ability to interact with aqueous biological matrices whilst retaining sufficient amphipathic character for membrane-proximal receptor engagement.
Physicochemical Summary Table
| Parameter | Value | Notes |
|---|---|---|
| Molecular Formula | C37H51N9O10S | Free base form |
| Molecular Weight | 887.93 g/mol | Average mass |
| CAS Number | 80714-61-0 | Confirmed by registry |
| Sequence | Met-Glu-His-Phe-Pro-Gly-Pro | ACTH(4–7)-PGP |
| Isoelectric Point (pI) | ~4.2 | Calculated |
| Understanding Semax within the broader landscape of synthetic neuropeptide research compounds requires a structured comparison of its defining analytical and physicochemical parameters against established benchmarks. The following table summarises four critical specification domains relevant to researchers selecting Semax as a reference or investigational compound within RUO laboratory settings.
Analytical Note: Core Research releases each Semax batch only upon satisfactory completion of both HPLC purity analysis and mass spectrometric identity confirmation. Batch-specific CoA documentation is available to verified research account holders upon request, providing full traceability from synthesis to dispatch. Regulatory Status and Safety ComplianceThe supply and handling of research-only compounds such as Semax within the United Kingdom operates within a clearly defined governance framework that Core Research adheres to without exception. All compounds catalogued under the RUO classification are supplied exclusively to verified institutional, academic, and licensed research purchasers. Core Research does not supply to private individuals for personal use, and all account verification processes are conducted in accordance with applicable UK regulatory guidance. From a regulatory compliance perspective, Semax is not a controlled substance under the Misuse of Drugs Act 1971 or the Psychoactive Substances Act 2016 in its current classification. However, researchers are advised to conduct their own institutional risk assessments and to consult their local ethics committees prior to initiating any experimental programme involving this compound. Compliance with COSHH (Control of Substances Hazardous to Health) regulations is mandatory for all laboratory handling procedures. Core Research’s internal governance framework incorporates data protection standards aligned with the UK General Data Protection Regulation (UK GDPR) and the Data Protection Act 2018. All customer and order data are processed on encrypted infrastructure, with access restricted to authorised personnel on a need-to-know basis. Research institutions handling compound-related data within their own systems are reminded of their independent obligations under UK GDPR, particularly where experimental data may intersect with identifiable participant information in translational research contexts. Safeguarding considerations are embedded within Core Research’s supply chain governance. The company maintains a zero-tolerance policy regarding the diversion of RUO compounds for human administration, and any communication suggesting intended human use will result in immediate order suspension and, where appropriate, referral to relevant statutory authorities. Researchers working in institutional settings are reminded that their own organisations’ safeguarding policies — whether pertaining to adult or child research participants — remain fully applicable and take precedence over any commercial relationship. Secure and confidential reporting mechanisms are available for any concerns relating to compound misuse, supply chain integrity, or governance breaches. Core Research maintains a dedicated compliance contact channel, and all reports are handled with strict confidentiality in accordance with whistleblowing best practice guidance. Researchers are encouraged to familiarise themselves with their institutional reporting pathways alongside Core Research’s own escalation procedures. Governance Reminder: Any researcher who becomes aware of Semax or any other RUO compound being used outside of an approved research context — including any suggestion of human self-administration — is strongly encouraged to report this through their institutional governance channels and, where appropriate, to relevant regulatory bodies including the MHRA. Research Questions and Technical SupportThe following questions represent the most substantive and technically grounded enquiries received by Core Research’s research support team regarding Semax. Each response is calibrated for researchers with a working knowledge of peptide biochemistry and neuropeptide pharmacology. What distinguishes Semax structurally from its parent ACTH(4–7) fragment?Semax appends a C-terminal Pro-Gly-Pro tripeptide to the ACTH(4–7) core sequence. This PGP extension confers conformational rigidity, substantially enhances enzymatic stability against prolyl endopeptidases, and modulates receptor binding geometry without introducing steroidogenic activity. Researchers consistently note this structural rationale as the compound’s most elegant design feature. Which melanocortin receptor subtypes does Semax interact with in pre-clinical models?Published pre-clinical data indicate primary interactions at MC4R and MC5R subtypes. MC4R engagement is associated with the compound’s documented effects on BDNF expression and cognitive-related behavioural endpoints in rodent models. MC5R interactions are less characterised but represent an active area of investigation. MC4R selectivity profiling remains a common research objective among enquiring investigators. How should Semax lyophilised powder be handled upon receipt in the laboratory?Upon receipt, lyophilised Semax should be equilibrated to ambient temperature before opening to prevent condensation-related degradation. Storage at −20 °C in a desiccated, light-protected environment is recommended. Reconstitution should be performed under inert conditions where possible to minimise methionine oxidation risk. Improper equilibration before opening is the most frequently reported handling error in our support enquiries. What analytical documentation accompanies each Core Research Semax batch?Each batch is released with a Certificate of Analysis documenting HPLC purity (≥98%), mass spectrometric identity confirmation, appearance, and batch-specific lot number. CoA documents are available to verified research account holders and are traceable to the specific synthesis and QC run. Researchers frequently cite CoA accessibility as a decisive factor in supplier selection. Is Semax suitable for use in cell-based receptor binding assays without organic co-solvents?Yes. Semax demonstrates excellent aqueous solubility exceeding 10 mg/mL in ultrapure water and PBS at pH 7.4, making it directly compatible with cell-based assay formats without requiring DMSO or ethanol co-solvents that could confound membrane receptor biology. This property is particularly valued by investigators running high-throughput melanocortin receptor screening panels. What is the regulatory status of Semax in the United Kingdom?Semax is not classified as a controlled substance under the Misuse of Drugs Act 1971 or the Psychoactive Substances Act 2016 in the UK. It is supplied exclusively as an RUO compound and is not licensed as a medicinal product by the MHRA. Institutional ethics approval remains the researcher’s independent responsibility. Regulatory status queries are among the most frequent pre-purchase enquiries we receive from UK academic institutions. Can Semax be used as a reference standard in BDNF expression studies?Semax has been employed in published pre-clinical studies as a pharmacological tool to investigate |