PUBLICATION
Novel use of FDA-approved drugs identified by cluster analysis of behavioral profiles
- Authors
- Tucker Edmister, S., Del Rosario Hernández, T., Ibrahim, R., Brown, C.A., Gore, S.V., Kakodkar, R., Kreiling, J.A., Creton, R.
- ID
- ZDB-PUB-220423-2
- Date
- 2022
- Source
- Scientific Reports 12: 6120 (Journal)
- Registered Authors
- Creton, Robbert
- Keywords
- none
- MeSH Terms
-
- Alzheimer Disease*
- Animals
- Calcineurin
- Calcineurin Inhibitors*/pharmacology
- Cluster Analysis
- Cyclosporine/pharmacology
- Immunosuppressive Agents/pharmacology
- Tacrolimus/pharmacology
- Zebrafish
- PubMed
- 35449173 Full text @ Sci. Rep.
Citation
Tucker Edmister, S., Del Rosario Hernández, T., Ibrahim, R., Brown, C.A., Gore, S.V., Kakodkar, R., Kreiling, J.A., Creton, R. (2022) Novel use of FDA-approved drugs identified by cluster analysis of behavioral profiles. Scientific Reports. 12:6120.
Abstract
Repurposing FDA-approved drugs is an efficient and cost-effective approach in the development of therapeutics for a broad range of diseases. However, prediction of function can be challenging, especially in the brain. We screened a small-molecule library with FDA-approved drugs for effects on behavior. The studies were carried out using zebrafish larvae, imaged in a 384-well format. We found that various drugs affect activity, habituation, startle responses, excitability, and optomotor responses. The changes in behavior were organized in behavioral profiles, which were examined by hierarchical cluster analysis. One of the identified clusters includes the calcineurin inhibitors cyclosporine (CsA) and tacrolimus (FK506), which are immunosuppressants and potential therapeutics in the prevention of Alzheimer's disease. The calcineurin inhibitors form a functional cluster with seemingly unrelated drugs, including bromocriptine, tetrabenazine, rosiglitazone, nebivolol, sorafenib, cabozantinib, tamoxifen, meclizine, and salmeterol. We propose that drugs with 'CsA-type' behavioral profiles are promising candidates for the prevention and treatment of Alzheimer's disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping