Topic
CYP2C9 Substrate
About: CYP2C9 Substrate is a research topic. Over the lifetime, 3 publications have been published within this topic receiving 232 citations.
Papers
Journal Article•
TL;DR: Puerarin inhibited the activity of CYP CYP1A2 and CYP2D6 in a dose-dependent fashion in vitro.
Abstract: Objective To investigate the effects of puerarin on activities of cytochrome 1A2(CYP1A2)、CYP2C9、CYP2C19、CYP2D6和CYP3A4 in vitro.Methods Caffeine(a CYP1A2 substrate),Tolbutamide(a CYP2C9 substrate),mephenytoin(a CYP2C19 substrate),Metoprolol(a CYP2D6 substrate) and Midazolam(a CYP3A4 substrate) were used as probes respectively.The concentrations of the probe drugs and their metabolites were determined by HPLC.The effect of puerarin on activities of CYP1A2、CYP2C9、CYP2C19、CYP2D6 and CYP3A4 was detected through recombinant enzyme reaction system in vitro.Results Puerarin had no significant effects on the activities of CYP2C9,CYP2C19 and CYP3A4,but the lower concentration(0.1 mmol·L-1) decreased the activities of CYP1A2 by(48±9)%(P0.05),CYP2D6 by(61±8)%(P0.01);the higher concentration decreased the activities of CYP1A2 by(82±8)%P0.01),CYP2D6 by(88±6)%(P0.01).Conclusion Puerarin inhibited the activity of CYP CYP1A2 and CYP2D6 in a dose-dependent fashion in vitro.
1 citations
TL;DR: The role of Glu-216 in substrate recognition, along with Asp-301, by site-directed mutagenesis is evaluated, illustrating the central role of the negative charges provided by both residues in defining the specificity of CYP2D6 toward substrates containing a basic nitrogen.
TL;DR: An atomistic model of complete CYP2C9 in a dioleoylphosphatidylcholine membrane is constructed and evolved by molecular dynamics simulations in explicit water on a 100+ ns time-scale and agrees well with known experimental data about membrane positioning of cytochromes P450.
Abstract: Cytochrome P450 2C9 (CYP2C9) is a membrane-anchored human microsomal protein involved in the drug metabolism in liver. CYP2C9 consists of an N-terminal transmembrane anchor and a catalytic cytoplasmic domain. While the structure of the catalytic domain is well-known from X-ray experiments, the complete structure and its incorporation into the membrane remains unsolved. We constructed an atomistic model of complete CYP2C9 in a dioleoylphosphatidylcholine membrane and evolved it by molecular dynamics simulations in explicit water on a 100+ ns time-scale. The model agrees well with known experimental data about membrane positioning of cytochromes P450. The entry to the substrate access channel is proposed to be facing the membrane interior while the exit of the product egress channel is situated above the interface pointing toward the water phase. The positions of openings of the substrate access and product egress channels correspond to free energy minima of CYP2C9 substrate ibuprofen and its metabolite in ...
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2011 | 1 |
| 2007 | 1 |
| 2003 | 1 |