Figure 3: Phenotypic screen-based discovery platform.

Schematic of discovery platform for novel pain targets using omics-based nociceptor selective targets and phenotypic screen-based compounds that decrease nociceptor excitability. The screen can be modified to discover targets that prevent peripheral sensitization by conducting phenotypic screens after nociceptors have been sensitized with inflammatory mediators. Validated nociceptor selective targets can be screened against diversity chemical libraries to identify scaffolds that modulate the activity of desired sets of targets. Structural and drug-like properties of these compounds can be enhanced and diversified using machine language assisted algorithms. New molecules designed from lead scaffolds can be tested for selective activity on nociceptor excitability by phenotypic screens and patch-clamp electrophysiology. Promising compounds with desired target modulation profile can be tested on preclinical animal models for efficacy, ADMET properties and safety.