Dual Inhibitors Targeting Nav1.8 and Nav1.7 Channels
Molecular dynamics and rapid SAR-driven discovery
Background
• Nav1.7 and Nav1.8 are key mediators in pain transduction, and their combined inhibition has shown synergistic analgesic effects, driving efforts to develop dual inhibitors targeting both channels.
• However, the high homology among Nav channel subtypes presents a significant challenge in designing dual-target inhibitors with selective activity for specific subtypes.
Approach
Results
• 40 molecules were recommended to medicinal chemists, with 34 exhibiting druglikeproperties.
• The compounds were synthesized and evaluated within one month.
• The results confirmed that our approach successfully achieved dual inhibition of Nav1.8 and Nav1.7 while maintaining selectivity over Nav1.5.
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