ICE Bioscience Posters

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Voltage gated sodium channels are pivotal therapeutic targets implicated in a variety of disorders, including chronic pain, epilepsy, and cardiac arrhythmias. The discovery of modulators that selectively and effectively target specific sodium channel subtypes requires advanced screening methodologies capable of producing accurate and biologically relevant data. This report outlines a fully integrated in vitro platform designed to streamline and enhance the discovery of sodium channel modulators through a multi-step approach: 1). Preliminary Screening: State dependent assays to identify potent compounds with targeted activity; 2). Selectivity Profiling: Determination of isoform selectivity (Nav1.1–Nav1.8) and species-specific selectivity; 3). Secondary Screening: Use-dependent assays to provide biologically relevant insights into compound activity; 4). Primary Neuron-Based Assays: Evaluation of candidate compounds using dorsal root ganglion (DRG) neurons from mouse, rat, cynomolgus monkey and human models; 5). Safety Profiling: Comprehensive assessment of off-target liabilities using a safety panel. This Strategy enables the efficient identification and optimization of sodium channel modulators with superior specificity, efficacy, and safety profiles. By addressing critical challenges such as subtype selectivity and off-target effects, it facilitates the accelerated development of next-generation therapeutics targeting ion channels.