检索结果-南通市图书馆

Discovery of a tetrahydroisoquinoline-based cdk9-cyclin t1 proteineprotein interaction inhibitor as an anti-proliferative and anti-migration agent against triple-negative breast cancer cells

引用

Genes & Diseases 2022年第6期9卷 1674-1688页

作者： Shasha Cheng Guan-Jun Yang Wanhe Wang Dik-Lung Ma Chung-Hang Leung State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao SARPR China Department of Chemistry Hong Kong Baptist UniversityKowloon TongHong Kong SARPR China Institute of Medical Research Northwestern Polytechnical UniversityXi’anShaanxi 710072PR China Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao SARPR China

triple-negative breast cancer(tNBC)is a highly aggressive and metastasizing cancer that has the worst prognosis out of all breast cancer subtypes.the epithelial emesenchymal transition(EMt)and cancer stem cells(CSCs)have been proposed as important mechanisms underlying tNBC metastasis.cdk9 is highly expressed in breast cancer,including tNBC,where it promotes EMt and induces cancer cell stemness.In this study,we have identified a tetrahydroisoquinoline derivative(compound 1)as a potent and selective cdk9-cyclin t1 inhibitor via virtual screening.Interestingly,by targeting the AtP binding site,compound 1 not only inhibited cdk9 activity but also disrupted the cdk9-cyclin t1 proteineprotein interaction(PPI).Mechanistically,compound 1 reversed EMt and reduced the ratio of CSCs by blocking the cdk9-cyclin t1 interaction,leading to reduced tNBC cell proliferation and migration.to date,compound 1 is the first reported tetrahydroisoquinoline-based cdk9-cyclin t1 AtP-competitive inhibitor that also interferes with the interaction between cdk9 and cyclin t1.Compound 1 may serve as a promising scaffold for developing more selective and potent anti-tNBC agents.Our work also provides insight into the role of the cdk9-cyclin t1 PPI on EMt and CSCs and highlights the feasibility and significance of targeting cdk9 for the treatment of tNBC.

关键词： Cancer stem cells cdk9-cyclin t1 Epithelial mesenchymal transition Proteineprotein interaction(PPI) triple-negative breast cancer(tNBC)

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：