Protein: Protein Interaction Based Allosteric Modulators of Voltage-gated Na+ Channels

The nexus of protein:protein interactions (PPI) within the voltage-gated Na+ (Nav) channel is the molecular determinant of neuronal excitability and a converging node in the etiology of neuropsychiatric disorders, neurodegenerative diseases and peripheral channelopathies. These PPI are highly specific and flexible, and could be ideal scaffolds for probe and drug development. I will present initial phases of a drug discovery campaign based on an integrated in vitro-to-ex vivo pipeline targeting the PPI interface at the level of the Nav channel and its regulatory proteins, the intracellular fibroblast growth factors (iFGF11-14). Compounds from this campaign could lead to a new class of Nav channel allosteric modulators with broad applications for CNS and PNS disorders.