摘要
背景:细胞色素P450(CYP)酶是膜结合血红蛋白,在外源性物质的解毒,细胞代谢和体内平衡中起着关键作用。 CYP酶的诱导或抑制是药物 - 药物相互作用的主要机制。 CYP酶可通过受体依赖性机制由各种异生素和内源底物转录激活。 CYP酶抑制是基于代谢的药物 - 药物相互作用的主要机制。许多化疗药物由于其抑制或诱导CYP酶系统的能力而可引起药物相互作用。基于计算机模拟分析和验证的预测已经确定了几种调节CYP的微RNA。遗传多态性和CYP基因的表观遗传变化可能是导致疾病易感性和药物治疗效果的个体间和种族间变异的原因。 目的:本文综述了细胞色素P450结构,功能,药物遗传学,药物遗传学和临床意义的综合汇编。 结论:关于CYP亚型的底物,诱导剂和抑制剂的知识以及CYP酶的多态性可用于临床医生确定治疗策略,以及由CYP基因产物代谢的药物的治疗剂量。
关键词: 药物不良反应(ADRs),细胞色素P450,药物相互作用,遗传多态性,microRNA,月光蛋白,异生素。
图形摘要
Current Drug Targets
Title:Cytochrome P450 Structure, Function and Clinical Significance: A Review
Volume: 19 Issue: 1
关键词: 药物不良反应(ADRs),细胞色素P450,药物相互作用,遗传多态性,microRNA,月光蛋白,异生素。
摘要: Background: The cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins that play a pivotal role in the detoxification of xenobiotics, cellular metabolism and homeostasis. Induction or inhibition of CYP enzymes is a major mechanism that underlies drug-drug interactions. CYP enzymes can be transcriptionally activated by various xenobiotics and endogenous substrates through receptor-dependent mechanisms. CYP enzyme inhibition is a principal mechanism for metabolism- based drug-drug interactions. Many chemotherapeutic drugs can cause drug interactions due to their ability to either inhibit or induce the CYP enzyme system. Predictions based on in silico analyses followed by validation have identified several microRNAs that regulate CYPs. Genetic polymorphisms and epigenetic changes in CYP genes may be responsible for inter-individual and interethnic variations in disease susceptibility and the therapeutic efficacy of drugs.
Objective: The present review is a comprehensive compilation of cytochrome P450 structure, function, pharmacogenetics, pharmacoepigenetics and clinical significance.
Conclusion: Knowledge about the substrates, inducers, and inhibitors of CYP isoforms, as well as the polymorphisms of CYP enzymes may be used as an aid by clinicians to determine therapeutic strategy, and treatment doses for drugs that are metabolized by CYP gene products.
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Cytochrome P450 Structure, Function and Clinical Significance: A Review, Current Drug Targets 2018; 19 (1) . https://dx.doi.org/10.2174/1389450118666170125144557
DOI https://dx.doi.org/10.2174/1389450118666170125144557 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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