Important role of CYP2J2 in protein kinase inhibitor degradation: a possible role in intratumor drug disposition and resistance

We have investigated in vitro the metabolic capability of 3 extrahepatic cytochromes P-450, CYP1A1, 1B1 and 2J2, known to be over-expressed in various tumors, to biotransform 5 tyrosine kinase inhibitors (TKI): dasatinib, imatinib, nilotinib, sorafenib and sunitinib. Moreover, mRNA expression of CYP...

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Veröffentlicht in:	PloS one 2014-05, Vol.9 (5), p.e95532-e95532
Hauptverfasser:	Narjoz, Céline, Favre, Amélie, McMullen, Justin, Kiehl, Philippe, Montemurro, Michael, Figg, William D, Beaune, Philippe, de Waziers, Isabelle, Rochat, Bertrand
Format:	Artikel
Sprache:	eng
Schlagworte:	Antibiotics Benzamides - metabolism Biology and Life Sciences Biopsy Cancer therapies Carcinoma, Hepatocellular - genetics Cell Line, Tumor Chromatography Cytochrome Cytochrome P-450 Cytochrome P-450 CYP1A1 - genetics Cytochrome P-450 CYP1B1 - genetics Cytochrome P-450 CYP2J2 Cytochrome P-450 CYP3A - genetics Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Cytochrome P450 Cytochromes Dasatinib Degradation Drug dosages Enzyme inhibitors Enzyme kinetics Gene amplification Gene expression Hep G2 Cells Humans Imatinib Imatinib Mesylate Indoles - metabolism Inhibition Kidney cancer Kinases Liver cancer Liver Neoplasms - genetics Mass spectrometry Medicine and Health Sciences Metabolism Metabolites Niacinamide - analogs & derivatives Niacinamide - metabolism Phenylurea Compounds - metabolism Physical Sciences Piperazines - metabolism Protein Kinase Inhibitors - metabolism Protein kinases Protein-tyrosine kinase Pyrimidines - metabolism Pyrroles - metabolism Renal cell carcinoma Reverse Transcriptase Polymerase Chain Reaction RNA Scientific imaging Sorafenib Sunitinib Thiazoles - metabolism Tissues Tumors Tyrosine Yang, Cindy β Lactamase
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