摘要
背景技术DNA拓扑异构酶II-α(Top2-α)是复制,转录,重组和染色质重塑中DNA的管理的必需酶,是最重要的抗癌靶标之一。许多分子被设计为Top2-α抑制剂。然而,一些研究已经显示Top2中的多态性和突变赋予了大多数这些抗癌药物的抗性。这项研究的目的是计算检查Top2-α基因组变异可能影响其对阿姆斯克和米托蒽醌作为酶的重要抑制剂的机制。 结果:结果表明,变异体K529E,R568H,R568G和T530M可能影响Atsacrine的Top2-α抑制作用,导致可能的耐药性。此外,R487K和Y481C变体可以改变酶对米托蒽醌的反应。 结论:这些结果可以促进Top2-α变体更有效的药物的预测和开发,使癌症化疗更有效果
关键词: 癌症治疗,耐药性,拓扑异构酶II,拓扑异构酶抑制剂,非同义多态性,对接。
Current Cancer Drug Targets
Title:Studies on Non-synonymous Polymorphisms Altering Human DNA Topoisomerase II-Alpha Interaction with Amsacrine and Mitoxantrone: An In Silico Approach
Volume: 17 Issue: 7
关键词: 癌症治疗,耐药性,拓扑异构酶II,拓扑异构酶抑制剂,非同义多态性,对接。
摘要: Background: DNA topoisomerase II-α (Top2-α), an essential enzyme for the management of DNA during replication, transcription, recombination, and chromatin remodeling, is one of the most important anticancer targets. Numerous molecules have been designed as Top2-α inhibitors. However, several studies have shown that polymorphisms and mutations in Top2 have conferred resistance to most of these anticancer drugs. The aim of this study was to computationally examine the mechanisms by which genomic variations in Top2-α could affect its resistance to Amsacrine and Mitoxantrone as important inhibitors of the enzyme.
Results: The results showed that variants K529E, R568H, R568G and T530M could affect Top2-α inhibition by Amsacrine causing possible drug-resistant. Moreover, R487K, and Y481C variants could change the response of the enzyme to Mitoxantrone. Conclusion: These results could facilitate the prediction and development of more effective drugs for Top2-α variants, making the cancer chemotherapy more effectivExport Options
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Cite this article as:
Studies on Non-synonymous Polymorphisms Altering Human DNA Topoisomerase II-Alpha Interaction with Amsacrine and Mitoxantrone: An In Silico Approach, Current Cancer Drug Targets 2017; 17 (7) . https://dx.doi.org/10.2174/1568009617666161109142629
DOI https://dx.doi.org/10.2174/1568009617666161109142629 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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