Selank Research, Specifications & Scientific Information

Selank is a synthetic heptapeptide consisting of the immunoglobulin-derived tetrapeptide tuftsin extended by a Pro-Gly-Pro tripeptide. It is registered as a pharmaceutical product in the Russian Federation and is not approved by the FDA for any indication.

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Category: Neuropeptides and cognitive research compounds

Introduction

Selank is a synthetic heptapeptide assembled from two parts that belong to different biological worlds. The first four residues are tuftsin — Thr-Lys-Pro-Arg — a peptide released by enzymatic cleavage from the heavy chain of immunoglobulin G, and a molecule of innate immunity rather than of the brain. The last three are Pro-Gly-Pro, added synthetically for stability, the same tail carried by Semax.

That hybrid origin explains something odd about the literature. A compound investigated principally as an anxiolytic also has a body of work on chemokine and cytokine gene expression in spleen [7], because the sequence it was built from was an immune peptide first. It also explains why its mechanism is contested: one line of evidence points at plasma peptidases and the enkephalin system [1], another at allosteric modulation of GABA binding [10], and a third study went looking for a transcriptional signature of the second and found nothing [9]. This page sets all three out, and says where each one stops.

What Is Selank?

Selank is a synthetic heptapeptide, sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro, written TKPRPGP in single-letter code. In the older literature — including papers that never use the name Selank — it appears as TP-7, and both designations refer to the same molecule.

It was developed in Russia at the Institute of Molecular Genetics together with the V.V. Zakusov Institute of Pharmacology, and it is registered there as a pharmaceutical product supplied as an intranasal preparation. It has not been approved by the U.S. Food and Drug Administration for any indication, no marketing application for it is on record in the United States, and no study of it is registered on ClinicalTrials.gov. A registration under one country's regulatory system establishes nothing under another's, and neither establishes anything about research-grade material supplied for laboratory work.

The parent peptide, tuftsin, was described in 1970 at Tufts University — which is where the name comes from — as a phagocytosis-stimulating fragment of immunoglobulin G. Tuftsin itself is short-lived; the Pro-Gly-Pro extension in Selank is the structural answer to that, and it is the single design decision that distinguishes the synthetic molecule from the natural one.

Selank Specifications

Compound name
Selank
Full chemical name
L-Threonyl-L-lysyl-L-prolyl-L-arginyl-L-prolylglycyl-L-proline
Aliases
TP-7, Thr-Lys-Pro-Arg-Pro-Gly-Pro, TKPRPGP, tuftsin analogue TP-7
Development code
TP-7
CAS number
129954-34-3
PubChem CID
11765600
UNII
TS9JR8EP1G
Compound type
Synthetic heptapeptide
Peptide family
Tuftsin analogues; proline-containing regulatory peptides
Amino acid sequence
TKPRPGP
Sequence length
7 residues
Molecular formula
C33H57N11O9
Molecular weight
751.9 g/mol
Primary target
No high-affinity receptor is established. The best-characterised molecular interactions are inhibition of plasma enkephalin-degrading enzymes and allosteric modulation of GABA binding to brain membrane preparations.
Secondary targets
Not publicly characterised
Receptor family
Tuftsin, the parent tetrapeptide, is a ligand at the neuropilin-1 and Fc-receptor-associated pathways of innate immunity; no corresponding receptor interaction has been established for this analogue.
Agonist / antagonist status
Not established; reported as a positive allosteric modulator of GABA binding in membrane preparations rather than as a receptor agonist or antagonist.

Selank is the endogenous tetrapeptide tuftsin — Thr-Lys-Pro-Arg, a fragment of the heavy chain of immunoglobulin G — extended at the C-terminus by the tripeptide Pro-Gly-Pro. That extension is the same structural device carried by Semax, the other peptide of this Russian series, and it exists for the same reason: the natural tetrapeptide is cleaved quickly in plasma, and the added tripeptide slows that cleavage. The identifiers here are the records held by PubChem (CID 11765600), which carries CAS registry number 129954-34-3 and FDA/NCATS UNII code TS9JR8EP1G. The formula and mass are for the free peptide; material supplied as an acetate or trifluoroacetate salt has a different measured mass and a different peptide content by weight. The development designation TP-7 appears throughout the older literature, including in papers that do not use the name Selank at all. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Selank Work?

There is no published binding constant for Selank at a named receptor, and the two mechanistic accounts in the literature operate at different levels of biology.

The enzymatic account is older and more concrete. Endogenous enkephalins are cleared from plasma by a set of peptidases collectively called enkephalinases; if those enzymes are inhibited, enkephalin persists longer. Selank inhibits them, and the argument is that its behavioural profile follows from raising endogenous enkephalin tone rather than from acting at any receptor itself [1].

The allosteric account is newer and sits closer to the pharmacology it is meant to explain. Clinical reports described a profile resembling that of classical benzodiazepines, which act as positive allosteric modulators at GABA-A receptors; radioligand work on isolated brain cell membranes subsequently described modulation of GABA binding consistent with that resemblance [10].

The two are not mutually exclusive, and neither is settled. What can be said without qualification is that a peptide built from an immunoglobulin fragment turns out to have measurable effects on inflammation-related gene expression [7] as well as on behaviour, and that any complete account will have to explain both.

Selank Mechanism of Action

In vitro research

Inhibition of enkephalin hydrolysis. In human plasma, Selank inhibited enzymatic hydrolysis of enkephalin with a half-maximal inhibitory concentration of 15 µM, and was more potent in that assay than the peptidase inhibitors bacitracin and puromycin. The same report noted that participants with generalised anxiety — but not those with panic disorder or agoraphobia — showed a shortened enkephalin half-life and reduced total enkephalinase activity in blood [1].

An inhibitory concentration of 15 µM is worth pausing on. It is micromolar, not nanomolar: this is not high-affinity pharmacology, and the figure belongs in any honest summary of the compound alongside the conclusion drawn from it.

Allosteric modulation of GABA binding. Using a radioligand binding method on isolated brain cell plasma membranes, Selank affected [3H]GABA binding in the manner of a positive allosteric modulator. Its joint action with benzodiazepines regulated GABA binding in a way that was not cumulative and differed from either substance alone, and it was able to block the modulatory activity of diazepam and of olanzapine. The authors read that as binding sites that are apparently not the same but may partially overlap, and describe the modulation as subtype-selective and concentration-dependent [10].

A negative result that belongs here. In cultured IMR-32 neuroblastoma cells, expression of 84 genes of the GABAergic system and of neurotransmission was measured by quantitative PCR under Selank, under GABA, under olanzapine, and under combinations. Selank alone produced no change in the messenger RNA levels of any gene studied. What it did do was suppress almost entirely the expression changes that GABA produced on its own, and amplify those produced by olanzapine [9].

That combination — no direct transcriptional effect, but a clear effect on what GABA does — is the strongest in vitro support the allosteric hypothesis has, and it is stronger precisely because the direct measurement came back empty.

What Is Selank Being Researched For?

  • Generalised anxiety disorder and neurasthenia — one randomised comparative clinical study conducted in Russia against an active benzodiazepine comparator [4].
  • Enkephalin and enkephalinase biochemistry — in human plasma and in mouse strains with differing stress phenotypes [1, 2].
  • GABAergic neurotransmission — membrane radioligand binding, gene expression in rat frontal cortex, and gene expression in a human neuroblastoma line [10, 8, 9].
  • Inflammation and immune gene expression — mouse spleen, reflecting the tuftsin origin of the sequence [7].
  • Neurotrophin regulation — BDNF expression in rat hippocampus after intranasal administration [5].
  • Rodent models of dependence and toxicity — naloxone-precipitated morphine withdrawal [12] and chronic ethanol exposure [11].

None of that is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Selank

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

The human evidence base is thin, and stating how thin is the most useful thing this section can do. One randomised comparative study is indexed in PubMed. It is in Russian, carries no digital object identifier, predates trial registration, and has not been replicated outside Russia.

Randomised comparison in generalised anxiety disorder and neurasthenia

Population. 62 participants with generalised anxiety disorder or neurasthenia, of whom 30 received Selank; the comparator was the benzodiazepine medazepam [4].

Endpoint. Anxiety and asthenia rating scales, including Zung and Clinical Global Impression instruments, with serum enkephalin activity measured alongside [4].

Result. The report describes the anxiolytic effects of the two compounds as similar, with Selank additionally showing antiasthenic and psychostimulant effects. On the biochemical side, participants with generalised anxiety disorder and neurasthenia had a reduced half-life of serum leu-enkephalin, which correlated with duration of illness and with the severity of anxiety, asthenia and autonomic symptoms; that parameter rose during treatment with Selank, most clearly in the generalised anxiety disorder group [4].

Limitations. Sixty-two participants in total and thirty in the index group; no placebo arm, only an active comparator; no registered protocol; no digital object identifier; a Russian-language full text that this summary has not assessed directly; and no independent replication. The biochemical correlation is the most interesting part of the report and is also the part most exposed to the small sample.

A second indexed human observation, reported inside a laboratory paper rather than as a clinical trial, is the finding that shortened enkephalin half-life and reduced enkephalinase activity distinguish generalised anxiety from panic disorder and agoraphobia [1]. It describes a patient population rather than an intervention, and it is what motivated the enzymatic hypothesis in the first place.

Preclinical Research on Selank

Animal research

Strain-dependent behaviour tied to a biochemical marker. BALB/c and C57Bl/6 mice differ at baseline in the half-life of plasma leu-enkephalin. At 100 µg/kg, Selank produced an anxiolytic effect in the open-field test and lengthened plasma leu-enkephalin half-life in BALB/c mice, and had no effect on either behaviour or enkephalinase activity in C57Bl/6 mice [2].

This is the most informative rodent result in the set, because the behavioural effect and the biochemical effect appear and disappear together, in the same strains. It is also a warning: a compound whose activity depends on the baseline phenotype of the animal will not behave uniformly across populations.

Comparison across the tuftsin family. Ten peptide compounds of the tuftsin family were compared against Selank in rats and in C57BL/6 and Balb/c mice grouped by type of emotional reactivity, in a conflict-situation model of emotional stress. Individual effects differed between the peptides and were attributed to their molecular structures and to their degradation fragments [3].

The attribution to degradation fragments recurs throughout this family of compounds and is not a throwaway remark: a short proline-rich peptide in biological media is a mixture, and what is measured may belong to a fragment rather than to the parent.

Neurotransmission gene expression in rat frontal cortex. Expression of 84 genes involved in neurotransmission — including the major GABA receptor subunit, transporters, ion channels and dopamine and serotonin receptors — was measured one and three hours after administration of Selank or of GABA. Forty-five genes changed expression at one hour and twenty-two at three hours, and the changes produced by Selank and by GABA at one hour were positively correlated [8].

Neurotrophins and inflammation. Intranasal administration regulates BDNF expression in rat hippocampus [5], and a transcriptomic response has been reported in rat hippocampus and spleen cells after both single and repeated administration [6]. Neither of those two reports carries an abstract in the PubMed record, so nothing quantitative is stated here from them; they are cited for the existence and location of the work, not for a number.

Findings described in this section were observed in rodents. Nothing in them establishes anything about humans.

Other Areas of Selank Research

Animal research

Two further rodent literatures deserve separate mention because they sit outside the anxiolytic frame the compound is usually discussed in.

Immune gene expression, the tuftsin inheritance. Expression of 84 inflammation-related genes — chemokines, cytokines and their receptors — was measured in mouse spleen six and twenty-four hours after a single intraperitoneal injection of 100 µg/kg of Selank or of two of its fragments. Thirty-four genes changed significantly. The gene Bcl6, a regulator of immune-system formation and development, responded to each of the peptides, and changes were also seen in its target and corepressor genes [7].

That the fragments were active too is the point worth carrying forward. It is direct evidence that this molecule's biology cannot be cleanly separated from the biology of what it breaks down into.

Morphine withdrawal. In outbred rats, a single intraperitoneal administration at 0.3 mg/kg reduced the total index of naloxone-precipitated morphine withdrawal by 39.6%, attenuated convulsive reactions, ptosis and posture disorders (p < 0.0001), and raised the tactile sensitivity threshold ninefold against active control. Diazepam at 2 mg/kg was somewhat more active on the same measures — a 49.3% reduction in the total index and a thirteenfold rise in sensitivity threshold [12].

Chronic ethanol exposure. Outbred rats given 10% ethanol as their only fluid for 30 weeks were tested for object recognition. Selank at 0.3 mg/kg daily for seven days by intraperitoneal injection acted on recognition performance in nine-month-old animals not exposed to ethanol (p < 0.05), prevented the formation of ethanol-associated memory and attention disturbance, and prevented the ethanol-associated rise in BDNF content in hippocampus and frontal cortex (p < 0.05) [11].

Note the direction of the BDNF result: ethanol raised BDNF and the peptide prevented that rise. Summaries that describe this compound as simply increasing BDNF are not describing this experiment.

Findings described in this section were observed in rodents, under specific models, at specific amounts. Nothing in them establishes anything about humans.

Current Research Status

Regulatory status (United States)
Not approved. Selank has not been approved by the U.S. Food and Drug Administration for any indication, and no marketing application for it is on record in the United States.
Investigational status
Registered and marketed as a pharmaceutical product in the Russian Federation, where it is supplied as an intranasal preparation. It is not the subject of any study registered on ClinicalTrials.gov, and no Western investigational programme is on record.
Highest research phase reached
A randomised comparative clinical study published in the Russian Federation; no phase-designated Western development programme exists.
Approved uses
Approved uses exist only under the Russian Federation's own registration, which is outside the scope of this page and confers nothing in the United States.
Approval is compound-specific
Yes

Status as of . This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Chemical & Molecular Characteristics

Selank is an unmodified seven-residue peptide with a free N-terminus and a free C-terminal carboxyl. PubChem carries it as compound identifier 11765600, with CAS registry number 129954-34-3 and FDA/NCATS UNII code TS9JR8EP1G. The recorded molecular formula is C33H57N11O9 and the average mass 751.9 g/mol.

Three prolines in seven residues. Positions 3, 5 and 7 are proline. A proline-rich sequence is conformationally constrained — proline is the only proteinogenic residue whose side chain closes back onto the backbone nitrogen — and it is also a poor substrate for many endopeptidases. Both the stability of the molecule and the difficulty of assigning it a conventional receptor pharmacology follow partly from that composition.

A basic peptide. Lysine at position 2 and arginine at position 4 give the molecule two strongly basic side chains and no acidic ones, so its isoelectric point is high and it carries net positive charge at physiological pH. That is characteristic of the tuftsin family and is relevant to how such peptides are handled analytically.

No sulfur, no aromatic residue. The sequence contains neither cysteine nor methionine, so there is no oxidation-sensitive residue, and it contains no tryptophan or tyrosine, which means it has very weak ultraviolet absorbance at 280 nm. Quantification and purity determination for this peptide therefore rely on peptide-bond absorbance near 214 nm or on mass spectrometry rather than on the 280 nm reading that suffices for many peptides — a practical point that belongs beside any purity figure.

Salt form changes the measured mass. The formula and mass above are for the free peptide. Acetate and trifluoroacetate salts have different measured masses and different peptide content by weight, which is one reason a catalogue figure and a certificate of analysis for a given lot are not interchangeable.

Analytical Specifications

Physical form
Lyophilized powder
Appearance
White to off-white lyophilized solid
Lot number
RP-2609-094
Tested purity
≥99% by HPLC
Storage
−20 °C, protect from light, desiccate

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

What is Selank?
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. The first four residues are tuftsin, a naturally occurring fragment of the heavy chain of immunoglobulin G; the trailing Pro-Gly-Pro is a synthetic addition that slows enzymatic cleavage. It was developed in Russia and appears in the older literature under the designation TP-7. It is registered as a pharmaceutical product in the Russian Federation and has not been approved by the U.S. Food and Drug Administration for any indication.
How does Selank work?
Two explanations coexist in the literature and neither has displaced the other. The older one is enzymatic: in human plasma the peptide inhibited hydrolysis of enkephalin with a half-maximal inhibitory concentration of 15 µM, more potently than bacitracin or puromycin [1]. The newer one is allosteric: radioligand work on isolated brain cell plasma membranes describes positive allosteric modulation of [3H]GABA binding, with an interaction against diazepam and olanzapine that is not additive [10]. A cell-culture study looking for a direct transcriptional signature of the second mechanism found none [9].
Is Selank FDA approved?
No. Selank has not been approved by the U.S. Food and Drug Administration for any indication, and no marketing application for it is on record in the United States. It is registered as a pharmaceutical product in the Russian Federation under that country's own regulatory system, which confers nothing elsewhere.
What is Selank studied for?
Its clinical literature is a single indexed randomised comparative study, conducted in Russia in generalised anxiety disorder and neurasthenia against the benzodiazepine medazepam [4]. Its experimental literature is larger and covers GABAergic and neurotransmission gene expression [8, 9], inflammation-related gene expression in spleen [7], neurotrophin regulation [5], and rodent models of opioid withdrawal [12] and chronic ethanol exposure [11].
What is tuftsin, and how does Selank relate to it?
Tuftsin is the tetrapeptide Thr-Lys-Pro-Arg, released by enzymatic cleavage from the heavy chain of immunoglobulin G, and it is a peptide of innate immunity rather than of the nervous system. Selank is tuftsin with a Pro-Gly-Pro tripeptide added to its C-terminus. That origin is why a compound studied largely as an anxiolytic also has a literature on chemokine and cytokine gene expression in spleen [7].
What is the difference between Selank and Semax?
They share the C-terminal Pro-Gly-Pro motif and the laboratory that produced them, and nothing else. Semax is built on a fragment of adrenocorticotropic hormone and its literature is dominated by neurotrophin expression and experimental cerebral ischaemia. Selank is built on tuftsin and its literature is dominated by GABAergic pharmacology and anxiolytic models. No study compares the two head to head.
Has Selank been compared with a benzodiazepine?
Yes, in one indexed study. Sixty-two participants with generalised anxiety disorder or neurasthenia were studied, 30 of them receiving Selank, against medazepam as the active comparator [4]. The report describes the anxiolytic effects of the two as similar. The full text is in Russian, the study carries no digital object identifier and no trial registration, and it has not been replicated outside Russia — so it should be read as one report, not as an established equivalence.
What identifiers are published for Selank?
CAS registry number 129954-34-3, PubChem compound identifier 11765600, and FDA/NCATS UNII code TS9JR8EP1G. The molecular formula recorded for the free peptide is C33H57N11O9 with an average mass of 751.9 g/mol, and the sequence is TKPRPGP.

Scientific References

  1. Zozulya AA, Kost NV, Yu Sokolov O, et al.. The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity Bulletin of experimental biology and medicine; 2001. PMID 11550013 doi:10.1023/a:1017979514274
  2. Sokolov OY, Meshavkin VK, Kost NV, et al.. Effects of Selank on behavioral reactions and activities of plasma enkephalin-degrading enzymes in mice with different phenotypes of emotional and stress reactions Bulletin of experimental biology and medicine; 2002. PMID 12432865 doi:10.1023/a:1015582302311
  3. Kozlovskaya MM, Kozlovskii II, Val'dman EA, et al.. Selank and short peptides of the tuftsin family in the regulation of adaptive behavior in stress Neuroscience and behavioral physiology; 2003. PMID 14969422 doi:10.1023/a:1025988519919
  4. Zozulia AA, Neznamov GG, Siuniakov TS, et al.. [Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia] Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova; 2008. PMID 18454096
  5. Inozemtseva LS, Karpenko EA, Dolotov OV, et al.. Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections; 2008. PMID 18841804 doi:10.1134/s0012496608040066
  6. Kolomin TA, Shadrina MI, Agniullin YV, et al.. Transcriptomic response of rat hippocampus and spleen cells to single and chronic administration of the peptide selank Doklady. Biochemistry and biophysics; 2010. PMID 20380151 doi:10.1134/s1607672910010023
  7. Kolomin T, Shadrina M, Andreeva L, et al.. Expression of inflammation-related genes in mouse spleen under tuftsin analog Selank Regulatory peptides; 2011. PMID 21609736 doi:10.1016/j.regpep.2011.05.001
  8. Volkova A, Shadrina M, Kolomin T, et al.. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission Frontiers in pharmacology; 2016. PMID 26924987 doi:10.3389/fphar.2016.00031
  9. Filatova E, Kasian A, Kolomin T, et al.. GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells Frontiers in pharmacology; 2017. PMID 28293190 doi:10.3389/fphar.2017.00089
  10. Vyunova TV, Andreeva L, Shevchenko K, et al.. Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity Protein and peptide letters; 2018. PMID 30255741 doi:10.2174/0929866525666180925144642
  11. Kolik LG, Nadorova AV, Antipova TA, et al.. Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats Bulletin of experimental biology and medicine; 2019. PMID 31625062 doi:10.1007/s10517-019-04588-9
  12. Konstantinopolsky MA, Chernyakova IV, Kolik LG. Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Signs of Morphine Withdrawal in Rats Bulletin of experimental biology and medicine; 2022. PMID 36322304 doi:10.1007/s10517-022-05624-x

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: Selank specifications and lot documentation