Fig. 1.

A schematic showing potential drug discovery strategies for identification of novel agents as future therapeutics for chronic kidney disease (CKD). There are 3 assay strategies for an initial (primary) screen. They all involve targeting 1 of the 3 key characteristics: cell shape, motility, and in vivo functionality. A podocyte cell-based phenotypic assay can be used to identify compounds that protect overall cellular cytoskeleton and morphology. A zebrafish-based assay can be used to screen compounds that would protect filtration barrier and kidney function. A 3rd type of assay, as described in the report by Tan et al. (5a), can be used to identify compounds that reduce injury-dependent increase in podocyte motility. Subsequently, the identified hits from each of the 3 types of campaigns could be validated in the other type of assay to select hits that affect these key podocyte qualities before testing in rodent experimental models. Selected compounds can then go through a few rounds of optimization, including target identification, mechanistic studies, and medicinal chemistry-based approaches, before entering a hit-to-lead program and be nominated as a therapeutic lead.