N-ribosyldihydronicotinamide:quinone oxidoreductase 2 (NQO2/QR2, Enzyme Commission number 1.10.99.2) is a cytosolic enzyme, abundant in the liver and variably expressed in mammalian tissues. Cloned 30 years ago, it was characterized as a flavoenzyme catalyzing the reduction of quinones and pseudoquinones. To do so, it uses exclusively N-alkyl nicotinamide derivatives, without being able to recognize NADH, the reference hydrure donor compound, in contrast to its next of a kind, NAD(P)H:quinone oxidoreductase 1 (NQO1). For a long time both enzymes have been considered as key detoxifying enzymes in quinone metabolism, but more recent findings point to a more toxifying function of NQO2, particularly with respect to ortho-quinones. In fact, during the reduction of substrates, NQO2 generates fairly unstable intermediates that reoxidize immediately back to the original quinone, creating a futile cycle, the byproducts of which are deleterious reactive oxygen species. Beside this peculiarity, it is a target for numerous drugs and natural compounds such as melatonin, chloroquine, imiquimod, resveratrol, piceatannol, quercetin, and other flavonoids. Most of these enzyme-ligand interactions have been documented by numerous crystallographic studies, and now NQO2 is one of the best represented proteins in the structural biology database. Despite evidence for a causative role in several important diseases, the functional role of NQO2 remains poorly explored. In the present review, we aimed at detailing the main characteristics of NQO2 from a molecular pharmacology perspective. By drawing a clear border between facts and speculations, we hope to stimulate the future research toward a better understanding of this intriguing drug target.

中文翻译：

---

NRH：醌氧化还原酶2的分子药理作用：一种作为底下的毒素酶的毒素。

N-核糖基二氢神经酰胺：醌氧化还原酶2（NQO2 / QR2，酶委员会编号1.10.99.2）是一种胞质酶，在肝脏中含量丰富，在哺乳动物组织中表达多样。它于30年前被克隆，其特征是一种黄酮酶，可催化还原醌和假醌。为此，它仅使用N-烷基烟酰胺衍生物，而不能识别NADH（参考水合供体化合物），而不是其下一个NAD（P）H：醌氧化还原酶1（NQO1）。长期以来，这两种酶都被认为是醌代谢中的关键排毒酶，但是最近的发现表明NQO2的排毒功能更强，尤其是对于邻甲醚而言。-醌。实际上，在还原底物期间，NQO2会生成相当不稳定的中间体，这些中间体会立即重新氧化回原来的醌，从而形成一个无用的循环，其副产物是有害的活性氧。除了这种特殊性，它还是许多药物和天然化合物（例如褪黑素，氯喹，咪喹莫特，白藜芦醇，苦味酚，槲皮素和其他类黄酮）的目标。大量的晶体学研究已证明了大多数这些酶-配体之间的相互作用，现在NQO2是结构生物学数据库中表现最好的蛋白质之一。尽管有证据表明在几种重要疾病中有致病作用，但对NQO2的功能性作用仍未充分探讨。在目前的评论中，我们旨在从分子药理学角度详细介绍NQO2的主要特征。通过在事实和推测之间划清界线，我们希望刺激未来的研究，以便更好地了解这个有趣的毒品目标。