Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Artículo científico |
| Language: | en |
| Published: |
Journal of medicinal chemistry
2024
|
| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39523548/ |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1868266282454876160 |
|---|---|
| author | Mao, Churu Fang, Jiebin Zou, Shijie Huang, Yun Chen, Xiaoming Ding, Xia Fang, Zhangyun Zhang, Ningjing Lou, Yijie Chen, Zhe Ding, Wanjing Ma, Zhongjun |
| author_facet | Mao, Churu Fang, Jiebin Zou, Shijie Huang, Yun Chen, Xiaoming Ding, Xia Fang, Zhangyun Zhang, Ningjing Lou, Yijie Chen, Zhe Ding, Wanjing Ma, Zhongjun Mao, Churu Fang, Jiebin Zou, Shijie Huang, Yun Chen, Xiaoming Ding, Xia Fang, Zhangyun Zhang, Ningjing Lou, Yijie Chen, Zhe Ding, Wanjing Ma, Zhongjun |
| collection | PubMed - marine biology |
| contents | Discovery of the First-in-Class Dual-Target ROCK/HDAC Inhibitor with Potent Antitumor Efficacy in Vivo That Trigger Antitumor Immunity. Mao, Churu Fang, Jiebin Zou, Shijie Huang, Yun Chen, Xiaoming Ding, Xia Fang, Zhangyun Zhang, Ningjing Lou, Yijie Chen, Zhe Ding, Wanjing Ma, Zhongjun Animals Humans Histone Deacetylase Inhibitors Mice Antineoplastic Agents Female Triple Negative Breast Neoplasms rho-Associated Kinases Cell Line, Tumor Cell Proliferation Protein Kinase Inhibitors Histone Deacetylases Structure-Activity Relationship Drug Discovery Drug Screening Assays, Antitumor Triple-negative breast cancer (TNBC) represents a highly aggressive and heterogeneous malignancy. Currently, multitarget drug approaches present a promising therapeutic approach for TNBC. Utilizing a combinatorial chemistry strategy to construct a virtual screening database, dual ROCK/HDAC-targeting benzothiophene compounds were identified. Notably, compound effectively inhibits ROCK1/2 and HDAC1/2/3/6/8 while demonstrating potent antiproliferative activity against breast cancer cells. In an orthotopic mouse model of breast cancer, significantly suppressed tumor growth without apparent toxicity. Importantly, induced immunogenic cell death (ICD), promoted dendritic cells (DCs) maturation, and activated T cells, thereby initiating antitumor immunity. In conclusion, compound is a novel dual-target ROCK/HDAC inhibitor that represents a promising treatment strategy for TNBC. |
| format | Artículo científico |
| id | pubmed_39523548 |
| institution | PubMed |
| language | en |
| publishDate | 2024 |
| publisher | Journal of medicinal chemistry |
| record_format | pubmed |
| spellingShingle | Discovery of the First-in-Class Dual-Target ROCK/HDAC Inhibitor with Potent Antitumor Efficacy in Vivo That Trigger Antitumor Immunity. Mao, Churu Fang, Jiebin Zou, Shijie Huang, Yun Chen, Xiaoming Ding, Xia Fang, Zhangyun Zhang, Ningjing Lou, Yijie Chen, Zhe Ding, Wanjing Ma, Zhongjun Animals Humans Histone Deacetylase Inhibitors Mice Antineoplastic Agents Female Triple Negative Breast Neoplasms rho-Associated Kinases Cell Line, Tumor Cell Proliferation Protein Kinase Inhibitors Histone Deacetylases Structure-Activity Relationship Drug Discovery Drug Screening Assays, Antitumor Discovery of the First-in-Class Dual-Target ROCK/HDAC Inhibitor with Potent Antitumor Efficacy in Vivo That Trigger Antitumor Immunity. Mao, Churu Fang, Jiebin Zou, Shijie Huang, Yun Chen, Xiaoming Ding, Xia Fang, Zhangyun Zhang, Ningjing Lou, Yijie Chen, Zhe Ding, Wanjing Ma, Zhongjun Animals Humans Histone Deacetylase Inhibitors Mice Antineoplastic Agents Female Triple Negative Breast Neoplasms rho-Associated Kinases Cell Line, Tumor Cell Proliferation Protein Kinase Inhibitors Histone Deacetylases Structure-Activity Relationship Drug Discovery Drug Screening Assays, Antitumor Triple-negative breast cancer (TNBC) represents a highly aggressive and heterogeneous malignancy. Currently, multitarget drug approaches present a promising therapeutic approach for TNBC. Utilizing a combinatorial chemistry strategy to construct a virtual screening database, dual ROCK/HDAC-targeting benzothiophene compounds were identified. Notably, compound effectively inhibits ROCK1/2 and HDAC1/2/3/6/8 while demonstrating potent antiproliferative activity against breast cancer cells. In an orthotopic mouse model of breast cancer, significantly suppressed tumor growth without apparent toxicity. Importantly, induced immunogenic cell death (ICD), promoted dendritic cells (DCs) maturation, and activated T cells, thereby initiating antitumor immunity. In conclusion, compound is a novel dual-target ROCK/HDAC inhibitor that represents a promising treatment strategy for TNBC. |
| title | Discovery of the First-in-Class Dual-Target ROCK/HDAC Inhibitor with Potent Antitumor Efficacy in Vivo That Trigger Antitumor Immunity. |
| topic | Animals Humans Histone Deacetylase Inhibitors Mice Antineoplastic Agents Female Triple Negative Breast Neoplasms rho-Associated Kinases Cell Line, Tumor Cell Proliferation Protein Kinase Inhibitors Histone Deacetylases Structure-Activity Relationship Drug Discovery Drug Screening Assays, Antitumor |
| url | https://pubmed.ncbi.nlm.nih.gov/39523548/ |