Cognition-related peptides in research: Semax, Selank and DSIP compared

Prepared by: Research Desk. Sources are linked for verification.

Overview

Semax, Selank and delta sleep-inducing peptide (DSIP) are short peptides that often appear together in neuroscience literature searches. They differ in origin, structure and depth of research record. This guide compares them using published studies and FDA records. Animal and cell results do not establish effects in people.

Separate pages cover Selank and DSIP in more detail.

Origins

Semax and Selank came out of a Moscow research programme on proline-rich peptides called glyprolines, associated with Igor Ashmarin and Nikolai Myasoedov. Semax was designed by groups at the Institute of Molecular Genetics of the Russian Academy of Sciences and Lomonosov Moscow State University. Selank was developed at the Institute of Molecular Genetics as an analogue of tuftsin, an endogenous immunomodulatory peptide. In a 2005 review, Ashmarin et al. argued that peptides carrying a Pro-Gly-Pro motif are far more stable in the body than most regulatory peptides. They described Semax and Selank as "hybrid" peptides that join a natural regulatory fragment to a stabilising glyproline tail.

DSIP has a separate history. Schoenenberger and Monnier reported isolating it from rabbit brain and characterising it in 1977. This work included its sequence and rabbit EEG experiments (Schoenenberger, 1977). FDA records refer to it as emideltide.

Sequences and structure

• Semax: Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues match positions 4 to 7 of ACTH, so the literature calls it an "ACTH(4-10) analogue" or "ACTH(4-7)PGP" (Eremin et al., 2005).
• Selank: Thr-Lys-Pro-Arg-Pro-Gly-Pro, a tuftsin-based sequence with the Pro-Gly-Pro tail.
• DSIP: Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, a nonapeptide with no glyproline tail.

Comparison table

What kinds of studies exist

Animal studies. In the sources used here, most Semax and Selank studies are in rats, with some cell work alongside them. For DSIP, the early record centres on rabbits. Monnier (1977) reported EEG and motor-activity observations. Another Monnier paper examined transport of synthetic DSIP across the blood–brain barrier (Monnier, 1977).

Cell and cell-free studies exist for both glyprolines. Filatova et al. (2017) reported that Selank alone did not change measured GABAergic gene mRNA levels in IMR-32 cells, while results differed in combination conditions. Sciacca et al. (2022) reported that Semax binds copper ions and interfered with copper-driven amyloid beta aggregation.

Human data for Semax are limited to small Russian-language studies. One example is an open-label, non-randomised study of 110 people after ischaemic stroke, which measured plasma BDNF and functional scores (Gusev et al., 2018). The sources used here include no human studies of Selank or DSIP.

Mechanisms proposed in preclinical work

Semax. Dolotov et al. (2003) reported raised BDNF expression in rat brain. Eremin et al. (2005) reported changes in a serotonin metabolite in rodent striatum. They also reported enhancement of D-amphetamine-induced dopamine release. In a rat arterial occlusion model, Filippenkov et al. (2020) reported 394 differentially expressed genes. In the same model, Sudarkina et al. (2021) reported changes in MMP-9, c-Fos, JNK and CREB. Liu et al. (2025) proposed the mu-opioid receptor as a possible target in mice. This single study has not been replicated.

Selank. Inozemtseva et al. (2008) reported that Selank regulated BDNF expression in rat hippocampus. Volkova et al. (2016) examined expression changes in neurotransmission-related genes in rat frontal cortex, including GABAergic genes.

DSIP. Early work linked DSIP to sleep-associated EEG patterns in rabbits, but its receptor and molecular mechanism remain unresolved. The original sleep-associated findings are not proof of a settled mechanism.

Recurring evidence limitations

• Originating-group concentration. A large share of Semax papers come from a few Moscow institutes. Many early Semax reports appeared in Russian-language journals or brief communications without full PubMed abstracts.
• Replication. Core Semax findings come mostly from the developing groups, and independent work is recent and limited.
• Model scope. Gene and protein changes in rodent tissue do not show what a peptide does in people.
• Human evidence. The sources identified no large randomised, placebo-controlled trials or systematic reviews of Semax.

Regulatory status in FDA records

FDA's page on bulk drug substances that may present significant safety risks covers category 2 under its interim compounding policies. It also lists nominations that were withdrawn by nominators. All three peptides appear on this page:

• Semax: "Semax (heptapeptide)" appears among the withdrawn nominations. FDA notes possible immunogenicity, aggregation, peptide-related impurities and limited safety information. Semax is not an FDA-approved drug.
• Selank: the page lists "Selank acetate (TP-7)". It notes an immunogenicity risk due to aggregation and peptide-related impurities, and states that FDA lacks safety information.
• DSIP: the page lists "Emideltide (DSIP)".

The agenda for the 23–24 July 2026 Pharmacy Compounding Advisory Committee meeting states that on 24 July 2026 the Committee would discuss emideltide (DSIP)-related and Semax-related bulk drug substances as candidates for the 503A Bulks List. The uses FDA evaluated were opioid withdrawal, chronic insomnia and narcolepsy for emideltide. For Semax, they were cerebral ischaemia, migraine and trigeminal neuralgia. Selank was not listed. This guide reports no outcome, and agenda listing is not approval.

Documentation researchers check for research material

• Certificate of analysis (COA): batch-specific identity, purity and methods.
• HPLC data: a chromatogram supporting the stated purity.
• Mass spectrometry (MS): an observed mass consistent with the expected sequence.
• Batch or lot number: matching across label, COA and analytical reports.

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Related pages

• Cognition-related peptides: a research reference
• About CognitivePepti
• Selank: the tuftsin analogue and its research record
• DSIP (delta sleep-inducing peptide): fifty years of an unresolved peptide