A novel preclinical strategy for identifying cardiotoxic kinase inhibitors and mechanisms of cardiotoxicity.

Abstract

Zebrafish may be a valuable preclinical tool to predict cardiotoxicity.

The α-adrenergic signaling pathway is an important modulator of sorafenib cardiotoxicity in vitro and in vivo and appears to act through a here-to-fore unrecognized signaling pathway downstream of α-adrenergic activation that bypasses Raf to activate ERKs.

Full Text

DOI - Circulation research (DOI)
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Subjects

Animals
Animals, Genetically Modified
Apoptosis
Benzenesulfonates
Cardiotoxins
Cell Survival
Cells, Cultured
Extracellular Signal-Regulated MAP Kinases
Female
Indoles
Male
Models, Animal
Myocytes, Cardiac
Protein Kinase Inhibitors
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-raf
Pyridines
Pyrroles
Quinazolines
Rats
Rats, Sprague-Dawley
Signal Transduction
Zebrafish

Authors

Publication date

2011-12-13

Journal

Circulation research
Circ Res (1524-4571)

Journal topics

Language

Eng.

Copyright

Circulation research

Center for Translational Medicine, the Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Release reference

Circ Res. 2011 Dec;109(12):1401-9