About: Interactions of Olomoucine II with Human Liver Microsomal Cytochromes P450.     Goto   Sponge   NotDistinct   Permalink

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  • Olomoucine II is a cyclin-dependent kinase inhibitor and a potential antineoplastic agent because it can arrest animal cell cycles. This study examines its interactions with human liver microsomal cytochrome P450 (P450) enzymes. Spectroscopic and high-performance liquid chromatography (HPLC) methods were used to estimate the degree of olomoucine II-mediated inhibition of enzymatic activities of eight drug-metabolizing P450s in vitro. In addition, mass spectrometry coupled with HPLC was used to identify an olomoucine II metabolite (2,5-dihydroxyroscovitine) formed in the reaction mixtures, and CYP3A4 was found to be responsible for the hydroxylation of the N6-benzyl ring at position 5, leading to this compound. Olomoucine II significantly inhibited the enzymatic activities of CYP1A2, CYP2C9, and (to a lesser degree) CYP3A4. The results indicate that use of olomoucine II as a drug could affect the activities of CYP3A4, CYP1A2, and CYP2C9 in vivo. Hence, the clinical relevance of these interactions shoul
  • Olomoucine II is a cyclin-dependent kinase inhibitor and a potential antineoplastic agent because it can arrest animal cell cycles. This study examines its interactions with human liver microsomal cytochrome P450 (P450) enzymes. Spectroscopic and high-performance liquid chromatography (HPLC) methods were used to estimate the degree of olomoucine II-mediated inhibition of enzymatic activities of eight drug-metabolizing P450s in vitro. In addition, mass spectrometry coupled with HPLC was used to identify an olomoucine II metabolite (2,5-dihydroxyroscovitine) formed in the reaction mixtures, and CYP3A4 was found to be responsible for the hydroxylation of the N6-benzyl ring at position 5, leading to this compound. Olomoucine II significantly inhibited the enzymatic activities of CYP1A2, CYP2C9, and (to a lesser degree) CYP3A4. The results indicate that use of olomoucine II as a drug could affect the activities of CYP3A4, CYP1A2, and CYP2C9 in vivo. Hence, the clinical relevance of these interactions shoul (en)
Title
  • Interactions of Olomoucine II with Human Liver Microsomal Cytochromes P450.
  • Interactions of Olomoucine II with Human Liver Microsomal Cytochromes P450. (en)
skos:prefLabel
  • Interactions of Olomoucine II with Human Liver Microsomal Cytochromes P450.
  • Interactions of Olomoucine II with Human Liver Microsomal Cytochromes P450. (en)
skos:notation
  • RIV/61989592:15110/09:00009613!RIV10-MSM-15110___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(GA301/08/1649), P(GD303/09/H048), Z(AV0Z50380511), Z(MSM6198959216)
http://linked.open...iv/cisloPeriodika
  • 6
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 319924
http://linked.open...ai/riv/idVysledku
  • RIV/61989592:15110/09:00009613
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • drug metabolism; antineoplastic drug; cytochrome P450 (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [A9D66B278548]
http://linked.open...i/riv/nazevZdroje
  • Drug Metabolism and Disposition
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 37
http://linked.open...iv/tvurceVysledku
  • Doležal, Karel
  • Strnad, Miroslav
  • Popa, Igor
  • Anzenbacher, Pavel
  • Anzenbacherová, Eva
  • Šiller, Michal
http://linked.open...n/vavai/riv/zamer
issn
  • 0090-9556
number of pages
http://localhost/t...ganizacniJednotka
  • 15110
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