The Janus kinase 2 inhibitor fedratinib inhibits thiamine uptake: a putative mechanism for the onset of Wernicke's encephalopathy

The clinical development of fedratinib, a Janus kinase (JAK2) inhibitor, was terminated after reports of Wernicke's encephalopathy in myelofibrosis patients. Since Wernicke's encephalopathy is induced by thiamine deficiency, investigations were conducted to probe possible mechanisms throug...

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Veröffentlicht in:	Drug metabolism and disposition 2014-10, Vol.42 (10), p.1656-1662
Hauptverfasser:	Zhang, Qiang, Zhang, Yan, Diamond, Sharon, Boer, Jason, Harris, Jennifer J, Li, Yu, Rupar, Mark, Behshad, Elham, Gardiner, Christine, Collier, Paul, Liu, Phillip, Burn, Timothy, Wynn, Richard, Hollis, Gregory, Yeleswaram, Swamy
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biological Transport, Active - drug effects Brain - metabolism Humans Janus Kinase 2 - antagonists & inhibitors Male Membrane Transport Proteins - drug effects Phosphotransferases (Phosphate Group Acceptor) - metabolism Protein Kinase Inhibitors - adverse effects Protein Kinase Inhibitors - blood Protein Kinase Inhibitors - pharmacokinetics Pyrrolidines - adverse effects Pyrrolidines - blood Pyrrolidines - pharmacokinetics Rats Sulfonamides - adverse effects Sulfonamides - blood Sulfonamides - pharmacokinetics Thiamine - metabolism Thiamine Deficiency - chemically induced Wernicke Encephalopathy - etiology Wernicke Encephalopathy - metabolism
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