Repression of PXR Function and CYP Expression under Pathologic and Physiologic Conditions

• 作 者: TaoshengChen;
• 机 构: High Throughput Screening St.Jude Children's Research Hospital USA
• 出 处: 中国上海第七届国际新药发明科技年会
• 发表日期: 2009年期

　　Changes in the level of drug-metabolizing enzymes,including CYPs,contribute to adverse drug-drug interactions.The expression of CYPs is significantly reduced under specific physiologic or pathologic conditions such as liver regeneration,infection and inflammation.PXR controls the expression of CYPs.The function of PXR can be attenuated through phosphorylation by protein kinases such as Cdk2,PKA,P70S6K and PKC,or via protein-protein interactions with other signaling molecules such as NF-κB.Attenuation of PXR function leads to the reduced expression of CYPs.These results have important implications in predicting and reducing drug-induced toxicity.The role of PXR antagonist in the regulation of PXR will also be discussed.