• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular cancer therapeutics >In silico screening reveals structurally diverse, nanomolar inhibitors of NQO2 that are functionally active in cells and can modulate NF-kappaB signaling.
【24h】

In silico screening reveals structurally diverse, nanomolar inhibitors of NQO2 that are functionally active in cells and can modulate NF-kappaB signaling.

机译：在计算机筛选中揭示了NQO2的结构多样的纳摩尔抑制剂，这些抑制剂在细胞中具有功能活性并可以调节NF-κB信号传导。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The National Cancer Institute chemical database has been screened using in silico docking to identify novel nanomolar inhibitors of NRH:quinone oxidoreductase 2 (NQO2). The inhibitors identified from the screen exhibit a diverse range of scaffolds and the structure of one of the inhibitors, NSC13000 cocrystalized with NQO2, has been solved. This has been used to aid the generation of a structure-activity relationship between the computationally derived binding affinity and experimentally measured enzyme inhibitory potency. Many of the compounds are functionally active as inhibitors of NQO2 in cells at nontoxic concentrations. To show this, advantage was taken of the NQO2-mediated toxicity of the chemotherapeutic drug CB1954. The toxicity of this drug is substantially reduced when the function of NQO2 is inhibited, and many of the compounds achieve this in cells at nanomolar concentrations. The NQO2 inhibitors also attenuated TNFalpha-mediated, NF-small ka, CyrillicB-driven transcriptional activity. The link between NQO2 and the regulation of NF-small ka, CyrillicB was confirmed by using short interfering RNA to NQO2 and by the observation that NRH, the cofactor for NQO2 enzyme activity, could regulate NF-small ka, CyrillicB activity in an NQO2-dependent manner. NF-small ka, CyrillicB is a potential therapeutic target and this study reveals an underlying mechanism that may be usable for developing new anticancer drugs.
机译：美国国家癌症研究所的化学数据库已通过计算机对接筛选，以鉴定NRH：醌氧化还原酶2（NQO2）的新型纳摩尔抑制剂。从筛选中鉴定出的抑制剂具有多种支架，并且已经解决了一种抑制剂NSC13000与NQO2共结晶的结构。这已被用于辅助在计算得出的结合亲和力和实验测量的酶抑制能力之间建立构效关系。许多化合物在细胞中以无毒浓度作为NQO2抑制剂的功能性活性。为了证明这一点，利用了化学治疗药物CB1954的NQO2介导的毒性。当NQO2的功能受到抑制时，该药物的毒性会大大降低，并且许多化合物在细胞中均以纳摩尔浓度达到此目的。 NQO2抑制剂也减弱了TNFalpha介导的NF-小ka和CyrillicB驱动的转录活性。 NQO2与NF-小钾，CyrillicB的调控之间的联系是通过使用短干扰RNA对NQO2进行的，并观察到NRH（NQO2酶活性的辅助因子）可以调节NQO2-的NF-小钾，CyrillicB活性。依赖方式。 NF-小钾，CyrillicB是潜在的治疗靶标，这项研究揭示了潜在的机制，可用于开发新的抗癌药物。

著录项

相似文献

  • 外文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号