Title : Human intestinal Raf kinase inhibitor protein , RKIP , catalyzes prasugrel as a bioactivation hydrolase
نویسندگان
چکیده
250 words Introduction: 315 words Discussion: 950 words Abbreviations: HPLC, high performance liquid chromatography; LC-MS/MS, liquid chromatography/tandem mass spectrometry; RKIP, Raf1-kinase inhibitor protein; HEPES, 2-[4-(2-Hydroxyethyl)-1-piperazinyl]ethanesulfonic acid; DMSO, dimethylsulfoxide ; Tris, tris(hydroxymethyl)aminomethane, SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis ; GFP, green fluorescent protein; prasugrel, 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyr idine; hCE, human carboxylesterase; thiolactone metabolite, 2-[2-oxo-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]-1-cyclopropyl-2-(2-fluorophenyl) ethanone; R-135766, (2Z)-(1-{2-[(2,2,3,3-H4)Cyclopropyl]-1-(2-fluorophenyl)-2-oxoethyl}-4-[( H3)methyls ulfanyl]piperidin-3-ylidene)ethanoic acid. This article has not been copyedited and formatted. The final version may differ from this version. DMD Fast Forward. Published on November 11, 2015 as DOI: 10.1124/dmd.115.066290 at A PE T Jornals on A ril 9, 2017 dm d.aspurnals.org D ow nladed from
منابع مشابه
Human Intestinal Raf Kinase Inhibitor Protein (RKIP) Catalyzes Prasugrel as a Bioactivation Hydrolase.
Prasugrel is a thienopyridine antiplatelet prodrug that undergoes rapid hydrolysis in vivo to a thiolactone metabolite by human carboxylesterase-2 (hCE2) during gastrointestinal absorption. The thiolactone metabolite is further converted to a pharmacologically active metabolite by cytochrome P450 isoforms. The aim of the current study was to elucidate hydrolases other than hCE2 involved in the ...
متن کاملDmd066290 115..123
Prasugrel is a thienopyridine antiplatelet prodrug that undergoes rapid hydrolysis in vivo to a thiolactone metabolite by human carboxylesterase-2 (hCE2) during gastrointestinal absorption. The thiolactone metabolite is further converted to a pharmacologically active metabolite by cytochrome P450 isoforms. The aim of the current study was to elucidate hydrolases other than hCE2 involved in the ...
متن کاملRaf kinase inhibitor protein , RKIP , catalyzes prasugrel as a bioactivation hydrolase
250 words Introduction: 315 words Discussion: 950 words Abbreviations: HPLC, high performance liquid chromatography; LC-MS/MS, liquid chromatography/tandem mass spectrometry; RKIP, Raf1-kinase inhibitor protein; HEPES, 2-[4-(2-Hydroxyethyl)-1-piperazinyl]ethanesulfonic acid; DMSO, dimethylsulfoxide ; Tris, tris(hydroxymethyl)aminomethane, SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel elec...
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Raf kinase inhibitor protein (RKIP) has been shown to be a suppressor of the mitogen-activated protein kinase pathway and is reported to be involved in human malignancy. However, the molecular mechanism of hepatitis B virus (HBV) in regulating RKIP expression is not yet clarified. In this study, we compared RKIP expression in 107 pairs of matched liver cancer and adjacent non-cancerous liver ti...
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Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor κB signaling that represses tumor invasion and metastasis. Glycogen synthase kinase-3β (GSK3β) suppresses tumor progression by downregulating multiple oncogenic pathways including Wnt signaling and cyclin D1 activation. Here, we show that RKIP binds GSK3 proteins and maintains GSK3β protein levels...
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