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Publication

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 optimization.

Investigators with authorship
Name Institution Mark P. de Caestecker Vanderbilt University

Complications
All Complications Bioinformatics Bone Cardiomyopathy Cardiovascular Gastro-Intestinal (GI) Nephropathy Neuropathy & Neurocognition Pediatric Endocrinology Retinopathy Uropathy Wound Healing