Supplementary Material for: Drug Discovery to Halt the Progression of Acute Kidney Injury to Chronic Kidney Disease: A Case for Phenotypic Drug Discovery in Acute Kidney Injury

The cellular responses that occur following acute kidney injury (AKI)
are complex and dynamic, involving multiple cells types and molecular
pathways. For this reason, early selection of defined molecular targets
for therapeutic intervention is unlikely to be effective in complex in
vivo models of AKI, let alone Phase 3 clinical trials in patients with
even more complex AKI pathobiology. Phenotypic screening using zebrafish
provides an attractive alternative that does not require prior
knowledge of molecular targets and may identify compounds that modify
multiple targets that might be missed in more traditional target-based
screens. In this review, we discuss results of an academic drug
discovery campaign that used zebrafish as a primary screening tool to
discover compounds with favorable absorption, metabolism, and toxicity
that enhance repair when given late after injury in multiple models of
AKI. We discuss how this screening campaign is being integrated into a
more comprehensive, phenotypic, and target-based screen for lead
compound optimization.