Drug Discovery to Halt the Progression of Acute Kidney Injury to Chronic Kidney
Disease: A Case for Phenotypic Drug Discovery in Acute Kidney Injury.
Authors Hukriede N, Vogt A, de Caestecker M
Submitted By Mark P. de Caestecker on 7/3/2017
Status Published
Journal Nephron
Year 2017
Date Published 6/15/2017
Volume : Pages Not Specified : Not Specified
PubMed Reference 28614822
Abstract 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

Investigators with authorship
Mark P. de CaesteckerVanderbilt University