Cognitive Stack (Semax + Selank)

Status of research: September 2026 · all sources with PubMed reference

What's included in the set

Both peptides are filled separately and are reconstituted separately. The set is an assembly of individual substances, not a premixed preparation.

Two peptides from the same school

Semax and Selank both originate from the Institute of Molecular Genetics of the Russian Academy of Sciences and follow the same design principle: a short endogenous peptide is extended with the sequence Pro-Gly-Pro , which protects it from rapid enzymatic degradation. In Semax, the parent molecule is a fragment of the adrenocorticotropic hormone without its hormonal activity; in Selank, the immune peptide tuftsin.

This shared origin matters for assessing the evidence: the literature on both substances originates predominantly from Russian institutions, has frequently been published in Russian-language journals, and consists mainly of cell-culture and rodent models. Neither Semax nor Selank holds a drug regulatory approval in the European Union or the United States. For the combination compiled here, there is no dedicated published study.

Semax: the first component

The best-documented observation on Semax concerns neurotrophic gene expression: Dolotov et al. (2006, Journal of Neurochemistry) and Dolotov et al. (2006, Brain Research) described effects on brain-derived neurotrophic factor (BDNF) and its receptor in the rat hippocampus. Kost et al. (2001) investigated the degradation of the peptide, which is essential for interpreting its short residence time.

A second line of work concerns the transcriptome analysis after cerebral ischemia: Dmitrieva et al. (2010), Shadrina et al. (2010), Filippenkov et al. (2020, Genes) and Filippenkov et al. (2024, Biomedicines) describe altered gene expression patterns in the rat model. Vyunova et al. (2023) and Inozemtseva et al. (2024, European Journal of Pharmacology) provide more recent mechanistic work; Panikratova et al. (2020) and Slominsky et al. (2017) provide context. The full account is available on the Semax product page.

Selank: the second component

Selank is the heptapeptide Thr-Lys-Pro-Arg-Pro-Gly-Pro, derived from the tuftsin fragment. The evidence primarily describes effects on anxiety and stress models and neurotransmitter systems: Zozulya et al. (2001) and Zozulya et al. (2008) reported clinical observations in anxiety disorders; Sokolov et al. (2002) and Semenova et al. (2009) investigated behavioral models in animals.

Mechanistically, two lines of work stand out. First, the gene expression in the brain: Kolomin et al. (2011), Kolomin et al. (2013) and Kolomin et al. (2014) described changes in immune and signaling genes. Second, the receptor level: Vyunova et al. (2018) investigated the binding properties, Inozemtseva et al. (2008) the effect on enzymatic activity. Siebert et al. (2017) provide a study from an independent group outside the original research environment. Further work concerns stress models (Volkova et al., 2016; Vasil’eva et al., 2016; Kolik et al., 2019) and inflammatory parameters (Filatova et al., 2017). The full account is available on the Selank product page.

Why the combination is being studied

The two peptides address different levels of the same system: Semax is mainly associated with neurotrophic gene expression and plasticity, while Selank is associated with the modulation of neurotransmitter systems and the stress response. This formally constitutes the constellation in which additivity would be expected — two sites of action, one shared endpoint in behavioral or memory models.

This expectation is a hypothesis, not a finding. Testing it requires four arms: control, Semax alone, Selank alone, combination. With behavioral endpoints, there is the added complication that they are particularly sensitive to experimental conditions — time of day, handling, cage changes, and test order can produce differences larger than the substance effect itself. Blinding and randomized test order are not optional here.

Why Pro-Gly-Pro is the actual design principle

Short peptides have a fundamental problem in the organism: they are broken down within minutes by aminopeptidases and carboxypeptidases. Russian neuropeptide research has developed its own answer to this, shared by both substances in this set — appending the sequence proline-glycine-proline to the active fragment.

Proline is a special case among amino acids: its side chain is connected to the backbone, which kinks the chain at this point and hinders access for peptidases. A proline at or near the end of the chain therefore acts like a lock. This principle is not limited to these two molecules, but is applied particularly consistently here: in both cases, the biologically active piece is a short endogenous fragment, and the appended segment serves purely for stability.

For experimental design, this has two consequences. First, the residence time is longer than for the unmodified fragment, but still short — hours should not be assumed. Second, degradation produces fragments that can have their own effects; a measured effect therefore does not automatically belong to the molecule administered. Anyone who wants to attribute a mechanism should know the degradation in their system, or at least choose the time of measurement so that the attribution remains plausible.

For experimental design

• Four arms, blinded. Without single-substance arms, no statement about additivity is possible; without blinding, behavioral data are weak.
• Plan for short residence time. Both peptides are rapidly degraded (Kost 2001); the interval between administration and test is a key variable and must be identical across all arms.
• Objective endpoints alongside behavioral ones. Gene expression, neurotrophic factors, and electrophysiological measures are less susceptible to experimenter effects than behavioral tests.
• Record the route of administration. The literature uses various routes; transferability between them is not established and should not be assumed.
• Keep the origin of the literature in mind. The evidence base originates predominantly from a single research tradition; independent replication is the most valuable contribution that one's own work can make here.
• Calculate on an equimolar basis. The two peptides have different molecular weights; a comparison by milligram compares different molar amounts.

What a replication study can contribute

The biggest shortcoming in the evidence for both peptides is not its quantity, but its concentration in a single research environment. A methodologically careful study outside this environment therefore has disproportionate value, and it need not be large to achieve this. Three things are decisive.

A pre-specified endpoint. Behavioral models offer many measures, and anyone who selects after the fact will almost always find something. Committing to a primary endpoint before the experiment begins is the most effective safeguard against self-deception.

An adequate group size. Behavioral data show strong variability; small groups produce both false-positive and false-negative results. Estimating the required number of animals from the expected effect size belongs at the start of planning, not at the end of the analysis.

A positive control. A model that does not respond to an established reference substance cannot deliver a reliable null result for the test substance either. The positive control demonstrates that the model worked on that day — and is what makes a negative result meaningful in the first place.

The blood-brain barrier as an open question

Any claim about the central nervous system effect of a peripherally administered peptide stands or falls on whether the molecule reaches its target tissue. For short, hydrophilic peptides, this cannot be taken for granted: the blood-brain barrier allows small lipophilic molecules to pass, while largely holding back charged and water-soluble ones unless a transporter takes them up.

For the two peptides in this set, the literature describes a central nervous system effect, but the route of uptake has not been conclusively established. Several possibilities are discussed: transport via carrier proteins, passage through regions without a complete barrier, uptake via the olfactory nerve with nasal administration, and an indirect effect via peripheral signals that are themselves processed centrally. These routes are not mutually exclusive and contribute to different extents depending on the route of administration.

Für die Versuchsplanung folgt daraus eine nüchterne Konsequenz: Ein zentralnervöser Endpunkt nach peripherer Gabe belegt noch nicht, dass die Substanz im Gehirn angekommen ist. Wer diesen Schritt belegen will, braucht eine Konzentrationsmessung im Zielgewebe oder im Liquor, ein markiertes Molekül oder zumindest den Vergleich verschiedener Applikationswege im selben Aufbau. Fehlt dieser Nachweis, ist die saubere Formulierung nicht „wirkt im Gehirn“, sondern „verändert einen zentralnervösen Endpunkt“ — ein Unterschied, der in der Peptidliteratur häufig verwischt wird.

Research applications

Sets of this composition are used in biomedical research in various contexts: (1) behavioral models of anxiety, stress, and learning in rodents; (2) gene expression analyses in the hippocampus and cortex; (3) neurotrophic factors and their receptors; (4) models of cerebral ischemia with transcriptome readout; (5) neurotransmitter systems (GABA, monoamines); (6) peptide stability and enzymatic degradation; (7) replication studies outside the original research environment; (8) analytical method development for short peptides in tissue and plasma.

Reconstitution and Yield

The information given applies exclusively to laboratory practice, not to any use in humans or animals.

For converting concentration, volume, and scale value, the Calculator available; recommended solvent for multiple withdrawals: bacteriostatic water. The current price is shown in the purchase box at the top of this page.

Quality: why every batch must be individually documented

For both peptides: HPLC purity and identity confirmed by mass spectrometry with its own batch number and its own certificate of analysis. For short, strongly hydrophilic peptides with several proline residues, two points are especially relevant: deletion sequences, in which one residue is missing and which differ in mass by the corresponding amount, as well as the net peptide content, because both peptides carry basic residues and are present as a salt — otherwise, the weighed-in mass systematically overestimates the peptide content. A combined certificate for the set does not replace the individual analyses.

Every ALPHASYNTH batch is tested by HPLC for purity and by Mass spectrometry for identity. The Certificate of Analysis (COA) is linked to the order and can be retrieved via the Vial Check using the batch designation; an overview of all reports is available at Lab Reports. How to read a COA is explained in the article How to read a Certificate of Analysis.

Specifications

Storage & Shelf Life

Laboratory Procedure

1. Bring both vials and the solvent to room temperature.
2. Disinfect the septa and allow to dry.
3. Use a fresh syringe for each peptide.
4. Add the solvent slowly along the inner wall, swirl gently, do not shake.
5. Visually inspect for clarity and absence of particles.
6. Note the concentration and date on each vial; store refrigerated.
7. In the experiment, combine the substances only at the point of preparation, and record the interval between administration and test.

Shipping & Handling

• Shipped by DHL from Germany, delivery within Germany typically 1–3 business days, within the EU 3–5 business days
• Discreet shipping, no product name on the package
• Lyophilizates are stable for transport for 2–3 days at room temperature; after receipt, store refrigerated or frozen
• Batch number on every vial, Certificate of Analysis (COA) available per batch

Related pages

• Semax · Selank — the individual substances with the full evidence base
• DSIP · Melatonin — adjacent fields of neurobiological research
• How to read a Certificate of Analysis — for sets, this applies per batch and peptide