PE 22-28: Scientific Profile

Publicado el 12 de julio de 2026 · Actualizado el 17 de julio de 2026

PE 22-28 (CAS 1801959-12-5) is a heptapeptide analog of spadin, designed as a blocker of the two-pore potassium channel TREK-1 (K2P/KCNK2). In research models it is studied for its ability to inhibit TREK-1, a mechanism associated with rapid-onset antidepressant-like behavior and neuronal plasticity. Product for research use only.

PE 22-28 is a short peptide (heptapeptide) belonging to the family of spadin analogs, a molecule derived from the propeptide of sortilin. Its chemical identity is well defined: CAS number 1801959-12-5, molecular formula C35H55N11O9, and molecular weight of approximately 773.89 g/mol. Within the categories of research compounds, it is commonly classified as a nootropic or neuromodulator, although its documented mechanism of action relates more specifically to the modulation of an ion channel implicated in models of affective behavior. It is important to emphasize from the outset that all available knowledge about PE 22-28 comes from preclinical studies —cell cultures, electrophysiology, and animal models— and that there are no clinical trials or approved therapeutic uses. This material is offered solely for research use.

To understand PE 22-28 it helps to start with spadin. Spadin is a peptide derived from the propeptide region (termed "PE") of sortilin, a receptor protein involved in intracellular trafficking and neurotrophic signaling. Academic research identified that this propeptide fragment acts as a specific blocker of the TREK-1 channel, a potassium channel of the two-pore-domain family (K2P, gene KCNK2). From spadin, shorter analogs were generated with the aim of preserving or improving activity on TREK-1 and of increasing metabolic stability against degradation by peptidases. PE 22-28 corresponds to the portion of the propeptide spanning residues 22 to 28, hence its name. In structure-activity studies, this heptapeptide segment was described as the minimal region capable of retaining the channel-blocking capacity, and some preclinical work reported an apparent affinity greater than that of full-length spadin, which made it a tool of interest for dissecting the role of TREK-1.

The proposed mechanism of action centers entirely on the TREK-1 channel. TREK-1 is a "leak" or background channel that contributes to maintaining the resting potential of the neuronal membrane; its opening hyperpolarizes the cell and reduces excitability. Research with genetically modified mice showed that the elimination of TREK-1 is associated with a phenotype resistant to depression-like behavior, which led to the proposal of pharmacological blockade of this channel as a strategy of interest in mood models. PE 22-28, by inhibiting the TREK-1-mediated potassium current, would in part mimic that loss-of-function phenotype. In animal models, this inhibition has been correlated with markers of plasticity: increased neurogenesis in the hippocampus, an increase in synaptogenesis markers, and a behavioral response of more rapid onset than that observed with serotonin reuptake inhibitors, which in the same paradigms require longer administration periods. It is essential to interpret these findings as observations in research models and not as effects demonstrated in humans.

The documented research applications for PE 22-28 therefore revolve around three axes. First, ion channel pharmacology: it is used as a probe to study the function of the TREK-1 channel and the K2P family by means of electrophysiology in heterologous expression systems and in neurons. Second, preclinical models of affective-type behavior, where it is used to explore the hypothesis that TREK-1 inhibition produces rapid-onset behavioral effects and to characterize the associated plasticity pathways. Third, exploratory lines of neuroprotection, since TREK-1 also participates in the neuronal response to ischemia and excitotoxicity; in this context, channel modulation is investigated with results that are still preliminary and sometimes dependent on the type of injury. These uses are strictly for the laboratory.

As for the level of evidence, honesty requires noting that PE 22-28 is a poorly characterized compound compared with established drugs. Most of the body of evidence on spadin and its analogs comes from a small number of academic research groups, mainly in a preclinical context. No human clinical trials supporting efficacy or safety have been completed, it has no regulatory approval as a medicine, and its pharmacokinetic, chronic toxicity, and whole-organism interaction profile remains incompletely described. For this reason the level of evidence is classified as preclinical, and any extrapolation to human applications would be speculative.

Regarding structure, PE 22-28 is a short linear peptide of seven residues. Given that there is some variability in how the exact sequence of these analogs derived from the sortilin propeptide is reported in the literature, this datasheet prefers not to assert a single-letter sequence that cannot be confirmed with certainty; the identity of the compound is supported by its CAS number, its molecular formula, and its molecular weight, which are the verified parameters. For work that requires the precise sequence, it is recommended to confirm it with the lot's analytical datasheet and with primary sources.

In summary, PE 22-28 is a research tool targeting the TREK-1 channel, derived from the spadina-sortilin propeptide lineage, with a clearly defined mechanism of action at the ion channel level but with an evidence base limited to the preclinical realm. Its interest lies in enabling the study of the role of K2P channels in neuronal excitability, plasticity, and models of affective behavior, always within a controlled experimental laboratory context.