For laboratory research use only. Not for human or veterinary use. This overview summarises the published research literature on Selank and Semax, two synthetic heptapeptides developed in Russia, along with related neuropeptides frequently discussed in the same context. It is intended as a reference for laboratory researchers and does not describe any use outside an in vitro or preclinical research setting.
Background: two peptides from one research programme
Selank and Semax both emerged from work at the Institute of Molecular Genetics of the Russian Academy of Sciences, where investigators explored how short, naturally occurring regulatory peptides could be modified to resist enzymatic degradation. The shared design strategy was to append a Pro-Gly-Pro (PGP) tripeptide to the C-terminus of a biologically active parent fragment. PGP itself is a collagen-derived motif, and its addition was reported to slow breakdown by peptidases in plasma and tissue preparations.
The two peptides differ in their parent fragments. Selank is built on tuftsin (Thr-Lys-Pro-Arg), an immunomodulatory tetrapeptide derived from the Fc region of immunoglobulin G. Semax is built on the ACTH(4-7) fragment (Met-Glu-His-Phe) of adrenocorticotropic hormone. Because of this shared PGP design but distinct parent sequences, the two are often grouped together in the literature, yet they were investigated for quite different research questions.
For a side-by-side structural comparison see Selank vs Semax: Structural and Research Differences. For detail on the melanocortin lineage of Semax see Semax as an ACTH(4-10) Analogue.
Selank: a tuftsin analogue
Tuftsin was first described in the early 1970s as a phagocytosis-stimulating peptide. It has a short half-life in biological fluids, which limits its usefulness as an experimental tool. By extending tuftsin with PGP, the Selank sequence (Thr-Lys-Pro-Arg-Pro-Gly-Pro) was produced as a more stable analogue for preclinical study.
GABAergic research findings
Much of the Selank literature concerns the GABAergic system. A 2016 study in Frontiers in Pharmacology by Volkova and colleagues reported that Selank administration in rodents was associated with changes in the expression of a number of genes involved in GABAergic neurotransmission in frontal cortex tissue. The authors discussed the possibility of an allosteric interaction with GABA-A receptors, while noting that the mechanism had not been fully characterised.
A 2017 paper in Behavioural Neurology by Kasian and colleagues examined Selank alongside diazepam in a rat model of unpredictable chronic mild stress. The study reported that co-administration altered behavioural measures compared with diazepam alone, and the authors interpreted this as consistent with an interaction at the level of GABAergic signalling. These findings come from animal models and should be read within that context.
Enkephalinase and immune research
Earlier Russian-language studies reported that Selank inhibited enkephalin-degrading enzymes in human serum in vitro, which was proposed as one route by which it might influence endogenous opioid peptide levels. Other work, consistent with its tuftsin origin, explored effects on cytokine gene expression in cell and animal models. These lines of enquiry remain less extensively replicated outside the originating research groups, which is an important caveat when designing new experiments.
Selank compound data
- Sequence: Thr-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP)
- Molecular formula: C33H57N11O9
- Molecular weight: approx. 751.9 g/mol
- CAS: 129954-34-3
- Form: lyophilised powder
- Storage: store lyophilised material at -20°C, protected from light and moisture
- Purity: >99% (see product page)
Research-grade Selank is available as Selank 10mg.
Semax: an ACTH-derived heptapeptide
Adrenocorticotropic hormone is a 39-residue peptide, and researchers had known since the mid-twentieth century that certain fragments, particularly ACTH(4-10), showed activity in behavioural assays without the steroidogenic effects of the full hormone. Semax combines ACTH(4-7) with PGP to give Met-Glu-His-Phe-Pro-Gly-Pro. It is commonly described as an ACTH(4-10) analogue because the PGP extension replaces the native residues 8 to 10 and was reported to extend stability.
Neurotrophin research
A frequently cited 2006 study in Brain Research by Dolotov and colleagues reported that Semax administration in rats was associated with increased expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus. This paper is often used as a starting point by groups investigating neurotrophin signalling with short peptides.
Ischaemia models and transcriptomics
Semax has also been studied in rodent models of focal cerebral ischaemia. A 2014 genome-wide transcriptional analysis published in BMC Genomics by Medvedeva and colleagues reported that Semax influenced the expression of genes associated with immune and vascular systems in ischaemic rat brain tissue. Such transcriptomic datasets are useful for generating hypotheses but do not by themselves establish mechanism.
Melanocortin receptor context
Because Semax derives from ACTH, researchers have asked whether it interacts with melanocortin receptors. Published discussion suggests that some ACTH fragments bind MC receptors, but Semax lacks the full core required for strong activity at several subtypes, and its receptor pharmacology is still debated. Researchers interested in melanocortin receptor work more broadly may also consult our note on PT-141 and melanocortin receptor pharmacology.
Semax compound data
- Sequence: Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP)
- Molecular formula: C37H51N9O10S
- Molecular weight: approx. 813.9 g/mol
- CAS: 80714-61-0
- Form: lyophilised powder
- Storage: store lyophilised material at -20°C, protected from light and moisture
- Purity: >99% (see product page)
Research-grade Semax is available as Semax 10mg.
Compound data
Summary of the two primary peptides covered in this overview:
- Selank: TKPRPGP, C33H57N11O9, approx. 751.9 g/mol, CAS 129954-34-3
- Semax: MEHFPGP, C37H51N9O10S, approx. 813.9 g/mol, CAS 80714-61-0
- Form: lyophilised powder
- Storage: -20°C, dry and protected from light
- Purity: >99% per product page
Related neuropeptides in the same research space
DSIP
Delta sleep-inducing peptide is a nonapeptide first isolated in 1977 from the cerebral venous blood of rabbits in which slow-wave sleep had been electrically induced. Its physiological role remains unresolved decades later. A dedicated summary is available in DSIP: Delta Sleep-Inducing Peptide in the Literature.
PT-141
PT-141 (bremelanotide) is a cyclic melanocortin receptor agonist derived from alpha-MSH analogues. It sits in the same broad melanocortin family as ACTH fragments and is a useful comparator when discussing receptor selectivity. See PT-141 and melanocortin receptor pharmacology.
Shared themes across the literature
Several recurring themes emerge when reading the Selank and Semax literature together. First, stability: both were designed to persist longer than their parent fragments, and much of the early work characterised degradation in plasma and brain homogenates. Second, gene expression: many of the more recent studies use transcriptomic or qPCR approaches to describe broad changes rather than identifying a single receptor target. Third, geography: a large proportion of the primary literature originates from a small number of Russian institutions, and independent replication in other countries is comparatively limited.
For experimental design, this means that researchers should be cautious when extrapolating from single studies. Where possible, published methods should be reproduced closely, including the animal strain, route used in the original model, and the timing of tissue collection. Negative and null results are reported less often than positive ones in this field, so the published picture may overstate consistency.
Analytical considerations for short peptides
Both peptides are small and hydrophilic, which makes reverse-phase HPLC with UV detection at around 214 to 220 nm a standard approach for purity assessment, typically paired with mass spectrometry to confirm identity against the theoretical monoisotopic mass. Semax contains methionine, which is susceptible to oxidation to methionine sulfoxide; an oxidised species appears as a +16 Da mass shift and can be a useful marker of storage-related degradation. Selank contains two prolines in the PGP tail and an arginine, which influence retention behaviour.
Researchers handling any of these materials typically document lot numbers, storage conditions and handling history so that results can be compared across experiments and laboratories. Consistency of material is one of the most common confounders in short-peptide work, because small sequences are susceptible to degradation by peptidases and to moisture uptake when stored poorly.
Peptide content and purity are distinct measurements. HPLC purity describes the proportion of the target peptide among UV-absorbing species, while net peptide content accounts for counter-ions such as acetate or trifluoroacetate and residual water. Researchers calculating molar concentrations for assays may wish to account for this difference in their own analytical workflow.
Storage and handling in the laboratory
Lyophilised peptides are generally most stable when kept frozen, dry and protected from light. Allowing vials to reach room temperature before opening limits condensation. Repeated freeze-thaw cycles of any prepared stock are commonly avoided in published methods by aliquoting. These are general laboratory practices rather than product-specific instructions, and individual laboratories should follow their own validated SOPs.
Historical context: regulatory peptides
Selank and Semax belong to a wider tradition of regulatory peptide research that gained momentum in the 1960s and 1970s. During that period, investigators such as David de Wied in the Netherlands reported that fragments of ACTH and vasopressin influenced behaviour in rodent conditioning paradigms independently of their classical endocrine actions. These findings encouraged the idea that short peptide fragments could act as signalling molecules in their own right within the central nervous system.
The main practical obstacle was stability. Natural short peptides are rapidly cleaved by aminopeptidases, carboxypeptidases and endopeptidases, often within minutes in plasma. Approaches to this problem included D-amino acid substitution, cyclisation, N-terminal acetylation and C-terminal amidation. The PGP extension used for Selank and Semax was a distinctive alternative, and one that retained an all L-amino acid sequence.
Understanding this history helps explain why so much of the early literature on both peptides concentrates on degradation kinetics, distribution in tissue homogenates and comparative stability against parent fragments, rather than on receptor binding studies of the kind that dominate modern pharmacology.
Considerations when designing comparative studies
Groups planning to study both peptides in parallel often consider matched molar concentrations rather than matched mass, since the molecular weights differ by roughly 60 g/mol. Including the parent fragments, tuftsin and ACTH(4-7), or the PGP tripeptide alone as controls can help to separate effects attributable to the parent sequence from those attributable to the stabilising tail. Vehicle controls, blinded scoring and appropriate power calculations are standard expectations for publication.
Because both peptides contain residues prone to chemical change, including methionine in Semax, analytical confirmation of identity at the start and end of a study can strengthen confidence that observed differences are not artefacts of degradation.
Gaps and open questions
- The primary receptor targets of Selank and Semax have not been definitively identified.
- Independent replication outside the originating institutions is limited.
- Many studies use gene expression endpoints, which describe association rather than mechanism.
- Comparative studies directly testing Selank against Semax in the same model are scarce.
- Pharmacokinetic data in peer-reviewed English-language journals are relatively sparse.
These gaps represent opportunities for well-designed preclinical work. Careful characterisation of material identity, transparent reporting of methods and pre-registration of hypotheses would all strengthen the evidence base in this area.
FAQs
What do Selank and Semax have in common?
Both are synthetic heptapeptides that end in the Pro-Gly-Pro motif, which was added to improve stability against peptidases. They were developed within the same Russian research programme.
How do they differ?
Selank is derived from tuftsin, an immunoglobulin fragment, while Semax is derived from the ACTH(4-7) fragment. Their published research focuses differ accordingly, with Selank studied more in GABAergic and immune contexts and Semax in neurotrophin and ischaemia models.
Are these compounds approved medicines in the UK?
No. Compound Cave supplies them strictly as research chemicals for laboratory use only. They are not for human or veterinary use.
Where can I read more about each peptide?
See our supporting notes: Selank vs Semax, Semax as an ACTH(4-10) Analogue, DSIP and PT-141 and melanocortin receptor pharmacology.
References
- Volkova A, et al. (2016). Selank administration affects the expression of some genes involved in GABAergic neurotransmission. Frontiers in Pharmacology.
- Kasian A, et al. (2017). Peptide Selank enhances the effect of diazepam in reducing anxiety in unpredictable chronic mild stress conditions in rats. Behavioural Neurology.
- Dolotov OV, et al. (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research.
- Medvedeva EV, et al. (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.
- Schoenenberger GA, Monnier M. (1977). Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proceedings of the National Academy of Sciences USA.
- Kovalzon VM, Strekalova TV. (2006). Delta sleep-inducing peptide (DSIP): a still unresolved riddle. Journal of Neurochemistry.
For laboratory research use only. Not for human or veterinary use.