Neuropeptides

In-vitro and preclinical literature on Semax, Selank, DSIP, Pinealon, VIP: mechanisms, model systems and 25 PubMed-linked references.

✔ PubMed-linked citations ✔ In-vitro and preclinical only ✔ Research Use Only

Neuropeptides are short amino-acid chains that act as signaling molecules in the nervous system, typically through G-protein-coupled receptors or by allosteric modulation of ion-channel receptors, and many also carry immune and endocrine signaling roles. The compounds in this class span a wide range of origins: endogenous fragments and analogs of pituitary hormones (Semax, an ACTH(4-7)-Pro-Gly-Pro heptapeptide), tuftsin-derived synthetic heptapeptides (Selank), a nonapeptide originally isolated from rabbit cerebral venous blood (DSIP), a synthetic tripeptide of the Khavinson short-peptide family (Pinealon, Glu-Asp-Arg), and a 28-residue endogenous member of the secretin/glucagon superfamily (VIP). The preclinical literature is dominated by rodent behavioral and neurochemical studies, brain-region transcriptomics, hippocampal slice electrophysiology, receptor-expressing cell lines, and primary neuronal or immune-cell cultures. Several members (Semax, Selank, Pinealon) have been studied predominantly by Russian laboratories, and much of that work appears in Russian-language journals with English abstracts; VIP by contrast has a large international receptor-pharmacology literature including cryo-EM structures of its receptors.

This page collects 25 peer-reviewed references across 5 compounds. Every citation links to its PubMed record so the primary source can be read in full. The selection is limited to in-vitro, ex-vivo and preclinical animal studies and mechanistic reviews; human clinical literature is deliberately excluded because Liv Pure products are supplied for laboratory research only.

Semax

Also known as: ACTH(4-7)-Pro-Gly-Pro; Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP); synthetic ACTH(4-10) analog; melanocortin-derived heptapeptide

Molecular target or pathway: No single confirmed receptor. Reported activity includes allosteric modulation of GABA-receptor binding in rat brain membranes, modulation of striatal serotonergic and dopaminergic markers, altered expression of neurotrophin (BDNF), immune, vascular, and CREB/JNK/MMP-9 pathway genes and proteins in rat brain, and a 2025 docking/network-pharmacology study proposing the mu-opioid receptor (Oprm1) as a target.

Origin: Synthetic analog: the ACTH(4-7) fragment of adrenocorticotropic hormone extended with a C-terminal Pro-Gly-Pro tripeptide to increase resistance to proteolysis. Lacks corticotropic (steroidogenic) activity.

Semax was developed at the Institute of Molecular Genetics (Moscow) as a non-corticotropic melanocortin fragment. The preclinical literature is largely rodent-based and covers neurochemistry (monoamine turnover), genome-wide transcriptomics and proteomics in focal cerebral ischemia models, GABA-receptor binding in isolated brain membranes, and chronic-stress and neurodevelopmental paradigms. A clinical literature also exists in Russian-language journals but is excluded here; only mechanistic and preclinical work is cited.

Liv Pure supplies Semax as a lyophilized research reagent with a lot-specific certificate of analysis.

Selected references

Eremin KO et al. (2005). Neurochem Res. C57BL/6 mice, striatal tissue and microdialysis. Semax (0.15 mg/kg, i.p.) increased striatal tissue and extracellular 5-HIAA and potentiated D-amphetamine-evoked dopamine release and locomotor activity without altering basal dopamine levels. PMID 16362768 · DOI
Medvedeva EV et al. (2014). BMC Genomics. Wistar rat permanent MCAO, cortical transcriptome (microarray). Genome-wide analysis at 3 and 24 h after occlusion showed Semax-associated expression changes predominantly in immune-system genes (immunoglobulins, chemokines) and in genes related to vascular development and endothelial migration. PMID 24661604 · DOI
Sudarkina OY et al. (2021). Int J Mol Sci. Wistar rat transient MCAO, brain protein immunodetection. At 24 h after tMCAO, Semax administration was associated with increased active CREB in subcortical tissue and decreased MMP-9, c-Fos, and phosphorylated JNK in adjacent frontoparietal cortex. PMID 34201112 · DOI
Vyunova TV et al. (2023). Chem Biol Drug Des. Isolated rat brain plasma membranes ([3H]GABA binding) and rat acute restraint stress. ACTH(4-7)PGP (Semax) and related synthetic corticotropin fragments each altered [3H]GABA binding at high- and low-affinity sites in a peptide-specific manner, consistent with allosteric modulation of the GABA-receptor system. PMID 36828803 · DOI
Inozemtseva LS et al. (2024). Eur J Pharmacol. Sprague-Dawley rat chronic unpredictable stress. Daily i.p. Semax (60 nmol/kg) attenuated stress-associated anhedonia, adrenal hypertrophy, and the reduction in hippocampal BDNF, with no effect on forced-swim immobility. PMID 39442746 · DOI

Selank

Also known as: Thr-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP); tuftsin-Pro-Gly-Pro; synthetic tuftsin analog; glyproline heptapeptide

Molecular target or pathway: No single confirmed receptor. Reported activity includes enhancement of spontaneous GABAergic inhibitory postsynaptic currents in rat hippocampal CA1 neurons, modulation of GABA-dependent gene expression (rat frontal cortex, IMR-32 cells), changes in hippocampal BDNF expression, altered carboxypeptidase activity in nervous tissue, and cytokine modulation in stressed rats.

Origin: Synthetic analog: the endogenous immunomodulatory tetrapeptide tuftsin (Thr-Lys-Pro-Arg, derived from the Fc domain of IgG) extended with a C-terminal Pro-Gly-Pro tripeptide for metabolic stability.

Selank was developed at the Institute of Molecular Genetics and the Zakusov Institute of Pharmacology (Moscow) as a stabilized tuftsin derivative. The mechanistic literature centers on the hypothesis that it acts as an allosteric modulator of the GABAergic system, tested by hippocampal slice electrophysiology, qPCR panels of neurotransmission genes in rat cortex and neuroblastoma cells, and BDNF measurement after intranasal administration. Clinical anxiolytic studies exist but are excluded here in favor of the preclinical and in-vitro subset.

Liv Pure supplies Selank as a lyophilized research reagent with a lot-specific certificate of analysis.

Selected references

Inozemtseva LS et al. (2008). Dokl Biol Sci. Wistar rat, intranasal administration, hippocampal RT-PCR and immunoassay. Intranasal Selank was associated with changes in BDNF mRNA and protein expression in rat hippocampus in vivo. PMID 18841804 · DOI
Volkova A et al. (2016). Front Pharmacol. Rat frontal cortex, 84-gene neurotransmission qPCR panel. One and three hours after Selank or GABA (300 ug/kg), expression of 45 and 22 neurotransmission-related genes respectively was altered, with positively correlated profiles between the two compounds at 1 h. PMID 26924987 · DOI
Filatova E et al. (2017). Front Pharmacol. IMR-32 human neuroblastoma cells, qPCR. Selank alone did not change mRNA levels of 84 GABAergic-system genes, but co-application nearly abolished GABA-induced expression changes and augmented olanzapine-induced changes. PMID 28293190 · DOI
Povarov IS et al. (2017). Bull Exp Biol Med. Wistar rat hippocampal slices, CA1 pyramidal neuron patch recording. Bath application of Selank (1-8 uM) increased the amplitude and frequency of spontaneous inhibitory postsynaptic currents, sometimes preceded by a transient decrease, without clear dose dependence in this range. PMID 28361410 · DOI
Kolik LG et al. (2019). Bull Exp Biol Med. Outbred rats with chronic ethanol exposure, ex vivo BDNF assay. Selank (0.3 mg/kg, 7 days, i.p.) prevented the ethanol-associated increase in BDNF content in hippocampus and frontal cortex and altered object-recognition performance. PMID 31625062 · DOI

DSIP (delta sleep-inducing peptide)

Also known as: Delta sleep-inducing peptide; Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE); nonapeptide; phosphorylated DSIP (p-DSIP) and KND analog are structural variants studied in the literature

Molecular target or pathway: No identified gene, precursor, or receptor. Reported activity includes naloxone-sensitive (mu-opioid antagonist-sensitive) effects on sleep architecture and hippocampal CREB phosphorylation, altered expression of antioxidant enzyme genes (Sod1, Gpx1), reduced hippocampal neuron responsiveness to lateral hypothalamic stimulation, and effects on hepatic oxidative-stress markers under restraint stress.

Origin: Originally isolated in 1977 from rabbit cerebral venous blood during induced sleep (Schoenenberger-Monnier group, Basel). Its endogenous origin remains uncertain; a 2006 review proposes that a DSIP-like peptide rather than DSIP itself accounts for measured immunoreactivity and activity.

DSIP is unusual among neuropeptides in that its sequence does not resemble any known peptide family and its gene and receptor have never been identified. The preclinical literature is mixed, with early sleep-promotion findings not consistently reproduced and later rodent work focusing on stress, oxidative-stress markers, antioxidant gene expression, and stroke models. Studies frequently use structural analogs (phosphorylated DSIP, KND), which should be distinguished from the parent peptide when interpreting results.

Liv Pure supplies DSIP (delta sleep-inducing peptide) as a lyophilized research reagent with a lot-specific certificate of analysis.

Selected references

Kovalzon VM et al. (2006). J Neurochem. Review. Reviewed the history of DSIP, noting the absence of an isolated gene, protein precursor, or receptor, and proposed that a DSIP-like peptide underlies observed immunoreactivity and biological activity. PMID 16539679 · DOI
Grigorchuk OS et al. (2012). Bull Exp Biol Med. Wistar rat dorsal hippocampus, in vivo single-unit recording with microiontophoresis. Microiontophoretic DSIP application reduced the proportion of dorsal hippocampal neurons responding to lateral hypothalamus stimulation from 37% to 28%. PMID 23113238 · DOI
Kutilin DS et al. (2014). Bull Exp Biol Med. Wistar rats aged 2-24 months, brain and nucleated blood cells, gene expression. Monthly 5-day courses of subcutaneous DSIP (100 ug/kg) were associated with increased Sod1 and Gpx1 expression in brain and blood cells across age groups. PMID 25257425 · DOI
Bobyntsev II et al. (2016). Bull Exp Biol Med. Wistar rat restraint stress, liver homogenate enzymology. DSIP at 40 ug/kg i.p. altered catalase and SOD activity and malondialdehyde concentration in liver under acute and chronic restraint stress, with effects lost at 360 ug/kg. PMID 26902351 · DOI
Roy K et al. (2018). Life Sci. Sprague-Dawley rat hypobaric hypoxia (7620 m), telemetric sleep recording, hippocampal Western blot. Phosphorylated DSIP (10 ug/kg, i.p.) altered NREM and REM sleep during chronic hypoxia and increased hippocampal p-CREB, and these effects were attenuated by the mu-opioid antagonist naloxone. PMID 30107169 · DOI

Pinealon

Also known as: Glu-Asp-Arg (EDR); EDR peptide; synthetic tripeptide of the Khavinson short-peptide (peptide bioregulator) family

Molecular target or pathway: No receptor identified. Proposed mechanism is nuclear penetration and sequence-preferential binding to DNA (CNG/CAG-containing oligonucleotides, major-groove interaction with guanine N7/O6 in physicochemical studies), with downstream changes in ERK1/2 activation, tryptophan hydroxylase and serotonin expression, antioxidant enzyme genes, and caspase-3.

Origin: Fully synthetic tripeptide designed by the St. Petersburg Institute of Bioregulation and Gerontology (Khavinson group); not an isolated endogenous fragment, though the sequence occurs within larger proteins.

Pinealon is one of a series of short 'regulatory peptides' whose literature comes predominantly from a single research network in St. Petersburg. In-vitro work covers reactive-oxygen-species accumulation and cell death in cerebellar granule cells, neutrophils and PC12 cells, FITC-labeled peptide uptake into HeLa nuclei, cell-free oligonucleotide binding, and serotonin expression in aging cortical cultures; in-vivo work includes 5xFAD mice, carotid occlusion in aged rats, and hypoxia models. Human geriatric studies exist but are excluded here; the citations below are the in-vitro, physicochemical, and preclinical subset.

Liv Pure supplies Pinealon as a lyophilized research reagent with a lot-specific certificate of analysis.

Selected references

Khavinson V et al. (2011). Rejuvenation Res. Rat cerebellar granule cells, neutrophils, and PC12 cells under oxidative stress. Pinealon dose-dependently restricted ROS accumulation and propidium-iodide-positive necrotic death, with a delayed time course of ERK1/2 activation and cell-cycle modification at higher concentrations. PMID 21978084 · DOI
Fedoreyeva LI et al. (2011). Biochemistry (Mosc). HeLa cells (FITC-labeled peptides) and cell-free fluorescence quenching with deoxyribooligonucleotides. FITC-labeled Glu-Asp-Arg localized to cytoplasm, nucleus and nucleolus, and intact peptide quenched labeled oligonucleotide fluorescence with sequence-dependent Stern-Volmer constants, preferentially for CNG/CAG-containing sequences. PMID 22117547 · DOI
Khavinson VKh et al. (2014). Bull Exp Biol Med. Aging Wistar rat cortical cell cultures; molecular docking. Glu-Asp-Arg and Lys-Glu-Asp increased serotonin expression in aging cortical cultures, and docking identified a CCTGCC sequence in the tryptophan hydroxylase gene as a candidate binding site. PMID 24909721 · DOI
Khavinson V et al. (2021). Pharmaceuticals (Basel). 5xFAD transgenic mice (i.p., 2-4 months of age) and DNA docking. EDR and KED peptides were associated with preserved dendritic spine density in 5xFAD mice, and docking predicted EDR binding sites in promoter regions of genes implicated in Alzheimer pathogenesis. PMID 34071923 · DOI
Khavinson V et al. (2020). Molecules. Review. Reviewed proposed molecular mechanisms of the EDR tripeptide, including cellular entry, binding to histones or nucleic acids, and effects on MAPK/ERK signaling, caspase-3, p53, SOD2, GPX1, PPARA/PPARG, serotonin and calmodulin expression. PMID 33396470 · DOI

VIP (vasoactive intestinal peptide)

Also known as: Vasoactive intestinal polypeptide; 28-amino-acid peptide (HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2); member of the secretin/glucagon/PACAP peptide superfamily

Molecular target or pathway: VPAC1 (VIPR1) and VPAC2 (VIPR2), class B G-protein-coupled receptors bound with high affinity; also recognizes PAC1 with low affinity. Primary coupling is Gs/adenylate cyclase/cAMP, with additional phospholipase C and calcium signaling reported depending on cell type. Cryo-EM structures of agonist-bound VPAC1 are available.

Origin: Endogenous neuropeptide, cleaved from the prepro-VIP precursor (which also yields PHI/PHM); expressed in central and peripheral neurons and in immune cells. Research material is synthetic peptide of the native sequence.

VIP is among the best characterized neuropeptides at the receptor level, with formal IUPHAR nomenclature for its receptors and structural data for VPAC1. The preclinical literature covers receptor pharmacology in transfected cell lines (COS-7, CHO, HEK293), cAMP and calcium mobilization assays, chimeric receptor mapping of ligand selectivity, and extensive immune-cell work in murine macrophages, dendritic cells and T cells where VIP acts through VPAC1/VPAC2 to modulate cytokine transcription. A substantial clinical and disease-focused literature exists but is not cited here; the references below are receptor-pharmacology reviews and in-vitro/preclinical mechanistic studies.

Liv Pure supplies VIP (vasoactive intestinal peptide) as a lyophilized research reagent with a lot-specific certificate of analysis.

Selected references

Harmar AJ et al. (2012). Br J Pharmacol. Review (IUPHAR nomenclature). Reviewed the structure, pharmacology and nomenclature of PAC1, VPAC1 and VPAC2 receptors, confirming that VPAC1 and VPAC2 respond to both VIP and PACAP with high affinity while PAC1 is PACAP-selective. PMID 22289055 · DOI
Lutz EM et al. (1999). Br J Pharmacol. COS-7 cells expressing chimeric VPAC2/PAC1 receptors, [125I]PACAP-27 binding and cAMP assays. Agonist selectivity between VIP and PACAP was determined primarily by the amino-terminal extracellular domain of the receptor, with additional domains influencing VIP and helodermin potency at PAC1-derived chimeras. PMID 10556928 · DOI
Delgado M et al. (1999). J Immunol. LPS-stimulated murine peritoneal macrophages in vitro and endotoxemic BALB/c mice. VIP and PACAP38 inhibited LPS-stimulated TNF-alpha production at the transcriptional level via VPAC1 and adenylate cyclase activation, and LPS or proinflammatory cytokines increased VIP release in serum and peritoneal fluid. PMID 9973516
Delgado M et al. (2011). Amino Acids. Review. Reviewed VIP production by neurons and immune cells, VIP receptor expression and signaling in macrophages, dendritic cells and CD4+ T cells, and involvement in inflammatory and autoimmune models. PMID 22139413 · DOI
Langer I et al. (2022). Biomedicines. Review (structural pharmacology). Reviewed molecular switches and interhelical interactions underlying VPAC1, VPAC2 and PAC1 activation, drawing on cryo-EM structures of agonist-bound VPAC1 and PAC1 and on splice-variant effects on agonist selectivity. PMID 35203615 · DOI

Frequently asked questions

What molecular targets have been proposed for the peptides in this class, and how well established are they?

The level of target characterization varies widely. VIP has the best-defined targets: it binds the class B GPCRs VPAC1 and VPAC2 with high affinity, coupling primarily to Gs and adenylate cyclase, and this is documented by IUPHAR nomenclature reviews and cryo-EM structures. Semax and Selank lack a single confirmed receptor; the literature reports allosteric modulation of [3H]GABA binding in brain membranes, changes in hippocampal transcription (including BDNF), and, for Semax, a recent docking/network-pharmacology study proposing the mu-opioid receptor. DSIP has no identified gene or receptor, and a 2006 review describes its mechanism as unresolved. Pinealon (Glu-Asp-Arg) has been studied for direct DNA/oligonucleotide interaction in cell-free and HeLa systems rather than receptor binding. Researchers should treat the non-VIP targets as hypotheses under investigation.

Which model systems appear in the literature for these peptides?

Common in-vitro models include rat hippocampal slices (spontaneous IPSC recording for Selank), isolated rat brain plasma membranes ([3H]GABA binding for ACTH-fragment peptides), IMR-32 and PC12 cell lines, rat cerebellar granule cells and cortical cultures (Pinealon), HeLa cells and cell-free DNA-binding assays (Pinealon), COS-7 cells expressing chimeric VPAC2/PAC1 receptors, and murine peritoneal macrophages (VIP). In-vivo work is mostly in Wistar, Sprague-Dawley, or outbred rats and C57BL/6 or BALB/c mice, using stress paradigms, middle cerebral artery occlusion, 6-OHDA lesions, 5xFAD transgenics, and endotoxemia, with readouts by qPCR, RNA-seq, microarray, Western blot, ELISA, HPLC monoamine analysis, and behavioral tests.

How should lyophilized neuropeptides be handled and stored in the laboratory?

General peptide-handling practice applies: keep lyophilized material sealed, desiccated, and frozen (-20 C or lower) and allow the vial to reach room temperature before opening to avoid condensation. Reconstitute in sterile, high-purity solvent appropriate to the peptide's charge (many of these sequences are water-soluble; acidic tripeptides such as Glu-Asp-Arg dissolve readily, while VIP is commonly reconstituted in dilute acetic acid or buffered saline with carrier protein to limit adsorption). Aliquot to avoid freeze-thaw cycles, use low-binding tubes for dilute solutions, and verify identity and purity by the supplier's certificate of analysis (HPLC/MS). Methionine-containing sequences such as Semax (Met-Glu-His-Phe-Pro-Gly-Pro) are susceptible to oxidation, so minimize exposure to air and light. Note that the published DSIP literature includes phosphorylated and structural analogs whose behavior differs from the parent nonapeptide.

All compounds referenced on this page are supplied by Liv Pure for in-vitro laboratory research only and are not for human or animal use. Nothing on this page is medical advice, and no statement here has been evaluated by the Food and Drug Administration. Product identity and purity for each lot are documented on the certificate of analysis; our Testing and Quality page explains what those certificates do and do not measure. Browse the Neuropeptides category to see current lots.

Neuropeptides

Semax

Selank

DSIP (delta sleep-inducing peptide)

Pinealon

VIP (vasoactive intestinal peptide)

Frequently asked questions

What molecular targets have been proposed for the peptides in this class, and how well established are they?

Which model systems appear in the literature for these peptides?

How should lyophilized neuropeptides be handled and stored in the laboratory?

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