PE-22-28

PE-22-28

PE-22-28 is a synthetic heptapeptide analogue of Spadin, a naturally occurring peptide derived from the propeptide of the TREK-1 potassium channel (TRAAK-related K+ channel). Spadin was identified as an endogenous antidepressant peptide that acts as a selective blocker of TREK-1, a two-pore domain (K2P) potassium channel implicated in mood regulation, nociception, and neuroprotection. PE-22-28 was developed as an optimised Spadin analogue with enhanced potency and selectivity for TREK-1, making it a refined research tool for investigating the role of K2P channels in neurological and psychiatric research.

Mechanism of Action

PE-22-28 selectively inhibits TREK-1 (KCNK2), a mechanosensitive and thermosensitive two-pore domain potassium channel widely expressed in the brain, particularly in regions associated with mood regulation including the hippocampus, prefrontal cortex, and raphe nuclei. TREK-1 blockade reduces the resting membrane hyperpolarisation in serotonergic neurons, increasing their excitability and enhancing serotonin release — a mechanism analogous to, but distinct from, classical antidepressant pharmacology. PE-22-28 has demonstrated rapid-onset antidepressant-like effects in preclinical models, and also promotes hippocampal neurogenesis via BDNF-dependent pathways.

Research Applications

• TREK-1 (K2P channel) pharmacology and selective inhibition studies
• Serotonergic neuron excitability and mood regulation research
• Rapid-onset antidepressant mechanism investigation
• Hippocampal neurogenesis and BDNF signalling research
• Nociception, mechanosensation, and neuroprotection modelling

Specifications

• Molecular Formula: C₃₅H₅₅N₁₁O₉
• Molecular Weight: 773.89 g/mol
• CAS Number: 1801959-12-5
• Purity: ≥98%
• Form: Lyophilised powder
• Storage: -20°C
• Shelf Life: 24 months

This product is intended for legitimate laboratory and analytical research use only. Not for diagnostic, therapeutic, or consumer use.