PUBLICATION
Validation of HDAC8 Inhibitors as Drug Discovery Starting Points to Treat Acute Kidney Injury
- Authors
- Long, K., Vaughn, Z., McDaniels, M.D., Joyasawal, S., Przepiorski, A., Parasky, E., Sander, V., Close, D., Johnston, P.A., Davidson, A.J., de Caestecker, M., Hukriede, N.A., Huryn, D.M.
- ID
- ZDB-PUB-220419-26
- Date
- 2022
- Source
- ACS pharmacology & translational science 5: 207-215 (Journal)
- Registered Authors
- Hukriede, Neil
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 35434532 Full text @ ACS Pharmacol Transl Sci
Citation
Long, K., Vaughn, Z., McDaniels, M.D., Joyasawal, S., Przepiorski, A., Parasky, E., Sander, V., Close, D., Johnston, P.A., Davidson, A.J., de Caestecker, M., Hukriede, N.A., Huryn, D.M. (2022) Validation of HDAC8 Inhibitors as Drug Discovery Starting Points to Treat Acute Kidney Injury. ACS pharmacology & translational science. 5:207-215.
Abstract
Acute kidney injury (AKI), a sudden loss of kidney function, is a common and serious condition for which there are no approved specific therapies. While there are multiple approaches to treat the underlying causes of AKI, no targets have been clinically validated. Here, we assessed a series of potent, selective competitive inhibitors of histone deacetylase 8 (HDAC8), a promising therapeutic target in an AKI setting. Using biochemical assays, zebrafish AKI phenotypic assays, and human kidney organoid assays, we show that selective HDAC8 inhibitors can lead to efficacy in increasingly stringent models. One of these, PCI-34051, was efficacious in a rodent model of AKI, further supporting the potential for HDAC8 inhibitors and, in particular, this scaffold as a therapeutic approach to AKI.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping