CYP3A4 和 CYP3A5 的差异调节及其在药物发现中的意义。
Differential Regulation of CYP3A4 and CYP3A5 and its Implication in Drug Discovery.
机构信息
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN, USA.
出版信息
Curr Drug Metab. 2017;18(12):1095-1105. doi: 10.2174/1389200218666170531112038.
BACKGROUND
Cancer cells use several mechanisms to resist the cytotoxic effects of drugs, resulting in tumor progression and invasion. One such mechanism capitalizes on the body's natural defense against xenobiotics by increasing the rate of xenobiotic efflux and metabolic inactivation. Xenobiotic metabolism typically involves conversion of parent molecules to more soluble and easily excreted derivatives in reactions catalyzed by Phase I and Phase II drug metabolizing enzymes.
METHODS
We performed a structured search of peer-reviewed literature on P450 (CYP) 3A, with a focus on CYP3A4 and CYP3A5.
RESULTS
Recent reports indicate that components of the xenobiotic response system are upregulated in some diseases, including many cancers. Such components include the pregnane X receptor (PXR), CYP3A4 and CYP3A5 enzymes. The CYP3A enzymes are a subset of the numerous enzymes that are transcriptionally activated following the interaction of PXR and many ligands.
CONCLUSION
Intense research is ongoing to understand the functional ramifications of aberrant expression of these components in diseased states with the goal of designing novel drugs that can selectively target them.
背景
癌细胞利用多种机制来抵抗药物的细胞毒性作用，导致肿瘤的进展和侵袭。其中一种机制是利用机体对异源生物的天然防御机制，增加异源生物的外排和代谢失活速度。异源生物代谢通常涉及母体分子在Ⅰ相和Ⅱ相药物代谢酶的催化下转化为更具水溶性和易排泄的衍生物。
方法
我们对 P450（CYP）3A 的同行评议文献进行了结构化检索，重点是 CYP3A4 和 CYP3A5。
结果
最近的报告表明，异源生物反应系统的一些成分在包括许多癌症在内的一些疾病中上调。这些成分包括孕烷 X 受体（PXR）、CYP3A4 和 CYP3A5 酶。CYP3A 酶是 PXR 与许多配体相互作用后转录激活的众多酶中的一个子集。
结论
目前正在进行大量研究，以了解这些成分在疾病状态下异常表达的功能后果，目的是设计能够选择性靶向这些成分的新型药物。
Zotero 插件