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.
- ID
- ZDB-PUB-170615-1
- Date
- 2017
- Source
- Nephron 137(4): 268-272 (Review)
- Registered Authors
- Hukriede, Neil
- Keywords
- Acute kidney injury, Drug discovery, Molecular targets, Phenotypic screening, Zebrafish
- MeSH Terms
-
- Acute Kidney Injury/drug therapy*
- Acute Kidney Injury/pathology
- Animals
- Disease Progression
- Drug Discovery*
- Humans
- Phenotype
- Renal Insufficiency, Chronic/drug therapy*
- Renal Insufficiency, Chronic/pathology
- Zebrafish
- PubMed
- 28614822 Full text @ Nephron
Citation
Hukriede, N., Vogt, A., de Caestecker, M. (2017) Drug Discovery to Halt the Progression of Acute Kidney Injury to Chronic Kidney Disease: A Case for Phenotypic Drug Discovery in Acute Kidney Injury. Nephron. 137(4):268-272.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping