A tyrosine kinase inhibitor-induced myocardial degeneration in rats through off-target phosphodiesterase inhibition

ABSTRACT PF‐04254644 is a selective kinase inhibitor of mesenchymal epithelial transition factor/hepatocyte growth factor receptor with known off‐target inhibitory activity against the phosphodiesterase (PDE) family. Rats given repeated oral doses of PF‐04254644 developed a mild to moderate myocardi...

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Veröffentlicht in:	Journal of applied toxicology 2012-12, Vol.32 (12), p.1008-1020
Hauptverfasser:	Hu, Wenyue, Hirakawa, Brad, Jessen, Bart, Lee, Michelle, Aguirre, Shirley
Format:	Artikel
Sprache:	eng
Schlagworte:	Activation Animals Biological and medical sciences Calcium Calcium - metabolism cardiotoxicity Cells, Cultured Cyclic AMP - metabolism Cyclic AMP Response Element-Binding Protein - genetics Dose-Response Relationship, Drug Gene Expression - drug effects Genes, Reporter Heart Inhibition Inhibitors Kinases Male Medical sciences Milrinone - pharmacology Myocardium - enzymology Myocardium - ultrastructure Myocytes, Cardiac - drug effects Myocytes, Cardiac - enzymology Myocytes, Cardiac - ultrastructure Oxidative stress Oxidative Stress - drug effects Partial differential equations Pathways PDE inhibition Phosphodiesterase Inhibitors - adverse effects Protein Kinase Inhibitors - adverse effects Quinolines - adverse effects Rats Rats, Sprague-Dawley Toxicology tyrosine kinase inhibitor
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