NAD(P)H:quinone oxidoreductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones.
NAD(P)H:quinone oxidoreductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones.
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DOI：
10.1016/j.bcp.2011.12.017
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发表时间：
2012-04-15
影响因子：
5.8
通讯作者：
Ross D
中科院分区：
文献类型：
--
作者：
Siegel D;Yan C;Ross D
醌药效团存在于许多药物类别中，但在抗肿瘤药物中特别常见。许多醌类化合物本质上是作为前药，还原后发挥其活性。醌的还原可以产生半醌或氢醌，随后产生活性氧自由基和氧化应激，醌可以被设计成当还原成氢醌时失去离去基团，产生反应性亲电试剂，或者分子的氢醌形式可以具有比母体醌更大的针对特定靶标的药理活性。因此，还原醌的酶系统在这类药物的药理活性中变得至关重要。存在许多可以催化醌还原的酶系统，包括细胞色素P450还原酶、细胞色素b5还原酶、NAD（P）H：醌氧化还原酶1（NQO 1）、NAD（P）H：醌氧化还原酶2（NQO 2）、羰基还原酶和硫氧还蛋白还原酶。在这种情况下，最广泛研究的还原酶之一是NAD（P）H：醌氧化还原酶1（NQO 1）。本文就NQO 1在临床上重要的醌类药物丝裂霉素C、β-拉帕醌和17 AAG的生物活化中的作用以及NQO 1 *2多态性对这些药物敏感性和耐药性的影响作一综述。
The quinone pharmacophore is present in many drug classes but is particularly common among antitumor drugs. Many quinones serve essentially as pro-drugs and exert their activities after reduction. Reduction of quinones may generate semiquinones or hydroquinones with subsequent generation of reactive oxygen radicals and oxidative stress, quinones can be designed so they lose a leaving group when reduced to the hydroquinone generating a reactive electrophile or the hydroquinone form of the molecule may have greater pharmacological activity than the parent quinone against a particular target. Enzyme systems that reduce quinones therefore become critically important in the pharmacological activity of this class of drugs. There are a number of enzyme systems that can catalyze reduction of quinones including cytochrome P450 reductase, cytochrome b5 reductase, NAD(P)H:quinone oxidoreductase 1 (NQO1), NAD(P)H:quinone oxidoreductase 2 (NQO2), carbonyl reductases, and thioredoxin reductase. In this context, one of the most extensively studied reductases has been NAD(P)H:quinone oxidoreductase 1 (NQO1). In this review we will focus on the role of NQO1 in the bioactivation of clinically important quinones mitomycin C, β-lapachone and 17AAG as well as the influence of the NQO1*2 polymorphism on the sensitivity and resistance to these agents.
DOI：
10.1111/j.1349-7006.1999.tb00785.x
发表时间：
1999-05
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Suzuki K;Yamamoto W;Park JS;Hanaoka H;Okamoto R;Kirihara Y;Yorishima T;Okamura T;Kumazaki T;Nishiyama M
通讯作者：
Nishiyama M