PE-22-28 (10mg)

PE-22-28 is a synthetic heptapeptide analog of spadin — itself a natural fragment of the sortilin propeptide — optimised for potent and selective antagonism of TREK-1 (KCNK2) two-pore domain potassium channels. TREK-1 is a background potassium channel highly expressed in limbic and serotonergic regions of the brain that acts as a "brake" on neuronal excitability. Its inhibition prolongs neuronal depolarisation, increases serotonergic neuron firing, and drives downstream CREB activation and BDNF expression.

PE-22-28 was designed to overcome spadin's pharmacokinetic limitations while maintaining its selectivity. With an IC50 of approximately 0.12 nM against TREK-1 — orders of magnitude more potent than spadin — PE-22-28 produces antidepressant-like behavioural effects in rodent models within 4 days, far faster than traditional SSRIs. It induces hippocampal neurogenesis, increases synaptogenesis markers (PSD-95, dendritic spine density), and elevates BDNF in preclinical studies.

In stroke models, PE-22-28 preserved dopaminergic neurons and prevented post-ischaemic depressive behaviour. Its high TREK-1 selectivity avoids off-target effects at cardiac (hERG), metabolic, or pain-related channels. As a rapidly acting neuroplasticity-promoting compound, PE-22-28 represents an emerging class of TREK-1-targeted neuropeptides with potential relevance in depression, cognitive decline, and neuroprotection research.