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首页> 外文期刊>Drug Target Insights >A Model for NAD(P)H:Quinoneoxidoreductase 1 (NQO1) Targeted Individualized Cancer Chemotherapy
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A Model for NAD(P)H:Quinoneoxidoreductase 1 (NQO1) Targeted Individualized Cancer Chemotherapy

机译：NAD（P）H：奎宁氧化还原酶1（NQO1）针对性的个体化癌症化疗的模型。

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摘要

NQO1 (NAD(P)H:quinoneoxidoreductase 1) is a reductive enzyme that is an important activator of bioreductive antitumor agents. NQO1 activity varies in individual tumors but is generally higher in tumor cells than in normal cells. NQO1 has been used as a target for tumor specific drug development. We investigated a series of bioreductive benzoquinone mustard analogs as a model for NQO1 targeted individualized cancer chemotherapy. We compared the tumor cell growth inhibitory activity of benzoquinone mustard analogs with sterically bulky groups of different size and placed at different positions on the benzoquinone ring, using tumor cell lines with different levels of NQO1. We demonstrated that functional groups of different steric size could be used to produce a series of bioreductive antitumor agents that were activated by different levels of NQO1 in tumor cells. This series of drugs could then be used to target cells with specific levels of NQO1 for growth inhibition and to avoid damage to normal cells, like bone marrow cells, that have low levels of NQO1. This approach could be used to develop new bioreductive antitumor agents for NQO1 targeted individualized cancer chemotherapy.
机译：NQO1（NAD（P）H：醌氧化还原酶1）是一种还原酶，是生物还原抗肿瘤剂的重要激活剂。 NQO1活性在单个肿瘤中有所不同，但通常在肿瘤细胞中要高于正常细胞。 NQO1已被用作肿瘤特异性药物开发的靶标。我们调查了一系列生物还原性苯醌芥菜类似物作为NQO1靶向个体化癌症化疗的模型。我们使用具有不同水平的NQO1的肿瘤细胞系，比较了具有不同大小的空间庞大基团并放置在苯醌环上不同位置的苯醌芥子类似物的肿瘤细胞生长抑制活性。我们证明了不同空间大小的官能团可用于产生一系列生物还原性抗肿瘤药物，这些药物可被肿瘤细胞中不同水平的NQO1激活。然后，该系列药物可用于靶向具有特定水平的NQO1的细胞，以抑制生长，并避免损害具有低水平NQO1的正常细胞，如骨髓细胞。该方法可用于开发针对NQO1靶向的个体化癌症化疗的新型生物还原抗肿瘤药。

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