治疗多发性骨髓瘤的蛋白酶体和 PARP1 双靶点抑制剂:氟唑帕尼

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kai Deng , Qiongqiong Li , Lina Lu , Luting Wang , Zhiyong Cheng , Suyun Wang
{"title":"治疗多发性骨髓瘤的蛋白酶体和 PARP1 双靶点抑制剂:氟唑帕尼","authors":"Kai Deng ,&nbsp;Qiongqiong Li ,&nbsp;Lina Lu ,&nbsp;Luting Wang ,&nbsp;Zhiyong Cheng ,&nbsp;Suyun Wang","doi":"10.1016/j.bbrep.2024.101781","DOIUrl":null,"url":null,"abstract":"<div><p>One of the current mainstream treatments for multiple myeloma (MM) is chemotherapy. However, due to the high clonal heterogeneity and genomic complexity of MM, single-target drugs have limited efficacy and are prone to drug resistance. Therefore, there is an urgent need to develop multi-target drugs against MM. We screened drugs that simultaneously inhibit poly(ADP-ribose) polymerase 1 (PARP1) and 20S proteasome through computer-aided drug discovery (CADD) techniques, and explored the binding mode and dynamic stability of selected inhibitor to proteasome through Molecular biology (MD) simulation method. Thus, the dual-target inhibition effect of fluzoparib was proposed for the first time, and the ability of dual-target inhibition and tumor killing was explored at the enzyme, cell and animal level, respectively. This provides a theoretical and experimental basis for exploring multi-target inhibitory drugs for cancers.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101781"},"PeriodicalIF":2.3000,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001456/pdfft?md5=562814c153e82dbbac7c67767214688c&pid=1-s2.0-S2405580824001456-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Proteasome and PARP1 dual-target inhibitor for multiple myeloma: Fluzoparib\",\"authors\":\"Kai Deng ,&nbsp;Qiongqiong Li ,&nbsp;Lina Lu ,&nbsp;Luting Wang ,&nbsp;Zhiyong Cheng ,&nbsp;Suyun Wang\",\"doi\":\"10.1016/j.bbrep.2024.101781\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>One of the current mainstream treatments for multiple myeloma (MM) is chemotherapy. However, due to the high clonal heterogeneity and genomic complexity of MM, single-target drugs have limited efficacy and are prone to drug resistance. Therefore, there is an urgent need to develop multi-target drugs against MM. We screened drugs that simultaneously inhibit poly(ADP-ribose) polymerase 1 (PARP1) and 20S proteasome through computer-aided drug discovery (CADD) techniques, and explored the binding mode and dynamic stability of selected inhibitor to proteasome through Molecular biology (MD) simulation method. Thus, the dual-target inhibition effect of fluzoparib was proposed for the first time, and the ability of dual-target inhibition and tumor killing was explored at the enzyme, cell and animal level, respectively. This provides a theoretical and experimental basis for exploring multi-target inhibitory drugs for cancers.</p></div>\",\"PeriodicalId\":8771,\"journal\":{\"name\":\"Biochemistry and Biophysics Reports\",\"volume\":\"39 \",\"pages\":\"Article 101781\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-07-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2405580824001456/pdfft?md5=562814c153e82dbbac7c67767214688c&pid=1-s2.0-S2405580824001456-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemistry and Biophysics Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2405580824001456\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemistry and Biophysics Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2405580824001456","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

化疗是目前治疗多发性骨髓瘤(MM)的主流疗法之一。然而,由于多发性骨髓瘤具有高度的克隆异质性和基因组复杂性,单靶点药物的疗效有限,而且容易产生耐药性。因此,开发针对 MM 的多靶点药物迫在眉睫。我们通过计算机辅助药物发现(CADD)技术筛选出同时抑制聚(ADP-核糖)聚合酶1(PARP1)和20S蛋白酶体的药物,并通过分子生物学(MD)模拟方法探讨了所选抑制剂与蛋白酶体的结合模式和动态稳定性。从而首次提出了氟唑帕尼的双靶点抑制作用,并分别从酶水平、细胞水平和动物水平探讨了氟唑帕尼的双靶点抑制和杀瘤能力。这为探索癌症多靶点抑制药物提供了理论和实验依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Proteasome and PARP1 dual-target inhibitor for multiple myeloma: Fluzoparib

One of the current mainstream treatments for multiple myeloma (MM) is chemotherapy. However, due to the high clonal heterogeneity and genomic complexity of MM, single-target drugs have limited efficacy and are prone to drug resistance. Therefore, there is an urgent need to develop multi-target drugs against MM. We screened drugs that simultaneously inhibit poly(ADP-ribose) polymerase 1 (PARP1) and 20S proteasome through computer-aided drug discovery (CADD) techniques, and explored the binding mode and dynamic stability of selected inhibitor to proteasome through Molecular biology (MD) simulation method. Thus, the dual-target inhibition effect of fluzoparib was proposed for the first time, and the ability of dual-target inhibition and tumor killing was explored at the enzyme, cell and animal level, respectively. This provides a theoretical and experimental basis for exploring multi-target inhibitory drugs for cancers.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
4.60
自引率
0.00%
发文量
191
审稿时长
59 days
期刊介绍: Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信