Selank and Semax are two synthetic heptapeptides developed from naturally occurring regulatory peptides. They are often discussed together because they share the same design idea: a short biologically active fragment, extended at the C-terminus with the tripeptide Pro-Gly-Pro. Beyond that shared tail, they come from different parent molecules and have been used to study different questions. This article compares their structures and the published research on each, so you can decide which one fits a neuroscience study.
Both compounds are supplied by BioSim for laboratory research only. They are not for human or veterinary use, and nothing here is guidance on administration to people.
A Shared Design: The Pro-Gly-Pro Extension
Short regulatory peptides such as tuftsin and ACTH fragments are broken down quickly by peptidases. Both Selank and Semax were designed by adding Pro-Gly-Pro to the C-terminus of the active fragment. Proline-rich sequences are less accessible to many common peptidases, and the extension was intended to lengthen the time the active fragment survives in experimental systems.
The result is two heptapeptides of similar size:
- Selank: Thr-Lys-Pro-Arg-Pro-Gly-Pro. The first four residues are tuftsin (Thr-Lys-Pro-Arg) (Zozulya et al., 2001).
- Semax: Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues are the ACTH(4-7) fragment (Dolotov et al., 2006).
Because the tail is shared, researchers comparing either heptapeptide with vehicle may want to include Pro-Gly-Pro alone as an extra control, to separate the effect of the active fragment from that of the tail.
Selank: A Tuftsin Analog
Tuftsin is a natural tetrapeptide (Thr-Lys-Pro-Arg) best known for its immunomodulatory activity. A review of tuftsin and its analogs describes dozens of derivatives studied for anti-inflammatory, antimicrobial and immune effects (Siebert et al., 2017). Selank is one of these analogs, and most published work on it has focused on anxiety-related behavior and neurotransmitter systems in rodents.
Three lines of research stand out:
- Enkephalin-degrading enzymes. Selank inhibited enzymatic hydrolysis of enkephalin in blood plasma in vitro, with an IC50 of about 15 µM, and was more potent than the peptidase inhibitors bacitracin and puromycin (Zozulya et al., 2001).
- GABAergic gene expression. In the rat frontal cortex, Selank changed the expression of 45 of 84 neurotransmission-related genes one hour after administration, and the pattern correlated with changes produced by GABA. The authors proposed allosteric modulation of the GABAergic system as one possible mechanism (Volkova et al., 2016).
- Behavioral models. In rats tested in the elevated plus maze under unpredictable chronic mild stress, Selank reduced anxiety-like indicators, and the combination with diazepam was the most effective condition under chronic stress (Kasian et al., 2017). In rats given ethanol for 30 weeks, Selank prevented ethanol-induced memory disturbances in an object-recognition test and prevented the ethanol-induced rise in hippocampal and frontal cortex BDNF (Kolik et al., 2019).
Semax: An ACTH(4-7) Analog
Semax is built from the N-terminal ACTH(4-7) sequence. The fragment does not include the part of ACTH needed to stimulate adrenal steroid release, so Semax is used to study central effects of the ACTH(4-10) family without the adrenal activation produced by full-length ACTH.
The best-characterized research area is neurotrophin signaling:
- BDNF and TrkB. In the rat hippocampus, a single application of Semax increased BDNF protein levels about 1.4-fold and TrkB tyrosine phosphorylation about 1.6-fold, along with increases in exon III BDNF and TrkB mRNA. Rats given Semax also showed more conditioned avoidance reactions (Dolotov et al., 2006).
- Ischemia transcriptomics. In a rat model of permanent middle cerebral artery occlusion, a genome-wide analysis found that Semax mainly enhanced the expression of immune-response genes, including immunoglobulin and chemokine genes, and also altered genes linked to the vascular system, at 3 and 24 hours (Medvedeva et al., 2014).
These findings make Semax a common tool for studying BDNF-dependent plasticity and the transcriptional response to experimental brain ischemia.
Side-by-Side Comparison
| Property | Selank | Semax |
|---|---|---|
| Sequence | Thr-Lys-Pro-Arg-Pro-Gly-Pro | Met-Glu-His-Phe-Pro-Gly-Pro |
| Molecular weight (approx.) | 751.9 Da | 813.9 Da |
| Parent peptide | Tuftsin (Thr-Lys-Pro-Arg) | ACTH(4-7) (Met-Glu-His-Phe) |
| Main research themes | Anxiety-related behavior, GABAergic gene expression, enkephalinase inhibition | BDNF/TrkB signaling, learning paradigms, ischemia transcriptomics |
| Typical models | Rat behavioral tests (elevated plus maze, object recognition), cortical gene-expression panels | Rat hippocampus, focal ischemia models, conditioned avoidance |
| Key references | Volkova et al., 2016; Kasian et al., 2017 | Dolotov et al., 2006; Medvedeva et al., 2014 |
The two peptides overlap in one area: both have been linked to BDNF. Semax raised hippocampal BDNF in naive rats (Dolotov et al., 2006), while Selank prevented an ethanol-induced change in BDNF (Kolik et al., 2019). The direction and context differ, so a study that measures BDNF with both compounds should use matched models and time points.
Choosing Between Them
Choose Selank when the study focuses on anxiety-related behavior, GABAergic signaling or the enkephalin system. Choose Semax when the endpoint is neurotrophin signaling, learning, or the transcriptional response to experimental ischemia. For a broader view of tools in this area, see our cognitive and neuroscience research overview, the guide to neuropeptides in research and the Neuropeptide Research category.
Most of the literature on both peptides comes from a small number of research groups, and much of it uses intranasal or intraperitoneal administration in rats. Independent replication in your own model, with appropriate vehicle and Pro-Gly-Pro controls, is good practice.
Stability and Handling in the Lab
Both peptides are supplied lyophilized. Reconstitute with a suitable sterile diluent, swirl gently rather than shaking, aliquot the stock to avoid repeated freeze-thaw cycles, and follow the storage conditions on the label. Semax contains methionine, which is prone to oxidation, so limit air exposure and avoid keeping solutions at room temperature longer than necessary. Our storage and stability guide covers these steps in more detail.
Frequently Asked Questions
Are Selank and Semax the same peptide with different names?
No. They share the C-terminal Pro-Gly-Pro extension, but Selank is built on tuftsin and Semax on the ACTH(4-7) fragment, so their N-terminal sequences and research profiles are different.
Which one has more published research on BDNF?
Semax has the more direct BDNF literature, including the hippocampal BDNF and TrkB data in rats (Dolotov et al., 2006). Selank has been studied mainly for GABAergic and behavioral endpoints.
How do I confirm the identity of my lot?
Every BioSim lot is third-party tested, with identity confirmed by mass spectrometry. Available certificates are published on our COA page.
References
- Dolotov OV, Karpenko EA, Inozemtseva LS, et al. (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. PMID: 16996037 · DOI: 10.1016/j.brainres.2006.07.108
- Kasian A, Kolomin T, Andreeva L, et al. (2017). Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats. Behavioural neurology, 2017, 5091027. PMID: 28280289 · DOI: 10.1155/2017/5091027
- Kolik LG, Nadorova AV, Antipova TA, et al. (2019). 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, 167(5), 641-644. PMID: 31625062 · DOI: 10.1007/s10517-019-04588-9
- Medvedeva EV, Dmitrieva VG, Povarova OV, 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, 15, 228. PMID: 24661604 · DOI: 10.1186/1471-2164-15-228
- Siebert A, Gensicka-Kowalewska M, Cholewinski G, et al. (2017). Tuftsin – Properties and Analogs. Current medicinal chemistry, 24(34), 3711-3727. PMID: 28745220 · DOI: 10.2174/0929867324666170725140826
- Volkova A, Shadrina M, Kolomin T, et al. (2016). Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Frontiers in pharmacology, 7, 31. PMID: 26924987 · DOI: 10.3389/fphar.2016.00031
- Zozulya AA, Kost NV, Yu Sokolov O, et al. (2001). The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity. Bulletin of experimental biology and medicine, 131(4), 315-7. PMID: 11550013 · DOI: 10.1023/a:1017979514274
Research These Compounds: Selank 10mg and Semax 10mg from BioSim Peptides: 99%+ purity, every lot third-party tested with identity confirmed by mass spectrometry, and available certificates published on our COA page. For laboratory research use only. Not for human consumption.
