Discovery of novel biphenyl compounds bearing hydroxamic acid moiety as the first PD-L1/class I HDACs dual inhibitors
Herein, we firstly reported a series of biphenyl compounds bearing hydroxamic acid moiety as PD-L1/class I HDACs dual inhibitors. Among them, compound 14 displayed the strongest inhibitory activity in vitro against HDAC2 and HDAC3 with IC50 values of 27.98 nM and 14.47 nM, and had an IC50 value of 8...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2025.2461190 |
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| author | Dandan Yuan Yali Gao Lin Xia Han Liu Xingye Wu Xueyan Ding Yudan Huang Changchun Deng Jin Li Wenqi Dai Jieqing Liu Junjie Ma |
| author_facet | Dandan Yuan Yali Gao Lin Xia Han Liu Xingye Wu Xueyan Ding Yudan Huang Changchun Deng Jin Li Wenqi Dai Jieqing Liu Junjie Ma |
| author_sort | Dandan Yuan |
| collection | DOAJ |
| description | Herein, we firstly reported a series of biphenyl compounds bearing hydroxamic acid moiety as PD-L1/class I HDACs dual inhibitors. Among them, compound 14 displayed the strongest inhibitory activity in vitro against HDAC2 and HDAC3 with IC50 values of 27.98 nM and 14.47 nM, and had an IC50 value of 88.10 nM for PD-1/PD-L1 interaction. Importantly, 14 could upregulate the expression of PD-L1 and CXCL10 in a PD-L1 low-expression cancer cell line (MCF-7), highlighting the potential to enhance efficacy by recruiting T-cell infiltration into TME and improving the response of PD-1/PD-L1 inhibitor associated with PD-L1 low-expression. Besides, we identified another compound, 22, which possessed the strongest inhibitory activity against PD-1/PD-L1 interaction with an IC50 value of 12.47 nM, and effectively inhibited the proliferation of three cancer cell lines. Our results suggest that compounds 14 and 22 can be served as lead compounds of PD-L1/class I HDACs dual inhibitors for further optimisation. |
| format | Article |
| id | doaj-art-2f6903321749470dbd34150ab00e5153 |
| institution | Kabale University |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-2f6903321749470dbd34150ab00e51532025-02-06T11:37:38ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742025-12-0140110.1080/14756366.2025.2461190Discovery of novel biphenyl compounds bearing hydroxamic acid moiety as the first PD-L1/class I HDACs dual inhibitorsDandan Yuan0Yali Gao1Lin Xia2Han Liu3Xingye Wu4Xueyan Ding5Yudan Huang6Changchun Deng7Jin Li8Wenqi Dai9Jieqing Liu10Junjie Ma11School of Medicine, Huaqiao University, Quanzhou, ChinaPharmacy Department, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, ChinaSchool of Medicine, Huaqiao University, Quanzhou, ChinaSchool of Medicine, Huaqiao University, Quanzhou, ChinaSchool of Medicine, Huaqiao University, Quanzhou, ChinaSchool of Medicine, Huaqiao University, Quanzhou, ChinaSchool of Medicine, Huaqiao University, Quanzhou, ChinaSchool of Medicine, Huaqiao University, Quanzhou, ChinaSchool of Medicine, Huaqiao University, Quanzhou, ChinaSchool of Medicine, Huaqiao University, Quanzhou, ChinaSchool of Medicine, Huaqiao University, Quanzhou, ChinaHerein, we firstly reported a series of biphenyl compounds bearing hydroxamic acid moiety as PD-L1/class I HDACs dual inhibitors. Among them, compound 14 displayed the strongest inhibitory activity in vitro against HDAC2 and HDAC3 with IC50 values of 27.98 nM and 14.47 nM, and had an IC50 value of 88.10 nM for PD-1/PD-L1 interaction. Importantly, 14 could upregulate the expression of PD-L1 and CXCL10 in a PD-L1 low-expression cancer cell line (MCF-7), highlighting the potential to enhance efficacy by recruiting T-cell infiltration into TME and improving the response of PD-1/PD-L1 inhibitor associated with PD-L1 low-expression. Besides, we identified another compound, 22, which possessed the strongest inhibitory activity against PD-1/PD-L1 interaction with an IC50 value of 12.47 nM, and effectively inhibited the proliferation of three cancer cell lines. Our results suggest that compounds 14 and 22 can be served as lead compounds of PD-L1/class I HDACs dual inhibitors for further optimisation.https://www.tandfonline.com/doi/10.1080/14756366.2025.2461190PD-1/PD-L1HDACdual inhibitorsbiphenylhydroxamic acid |
| spellingShingle | Dandan Yuan Yali Gao Lin Xia Han Liu Xingye Wu Xueyan Ding Yudan Huang Changchun Deng Jin Li Wenqi Dai Jieqing Liu Junjie Ma Discovery of novel biphenyl compounds bearing hydroxamic acid moiety as the first PD-L1/class I HDACs dual inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry PD-1/PD-L1 HDAC dual inhibitors biphenyl hydroxamic acid |
| title | Discovery of novel biphenyl compounds bearing hydroxamic acid moiety as the first PD-L1/class I HDACs dual inhibitors |
| title_full | Discovery of novel biphenyl compounds bearing hydroxamic acid moiety as the first PD-L1/class I HDACs dual inhibitors |
| title_fullStr | Discovery of novel biphenyl compounds bearing hydroxamic acid moiety as the first PD-L1/class I HDACs dual inhibitors |
| title_full_unstemmed | Discovery of novel biphenyl compounds bearing hydroxamic acid moiety as the first PD-L1/class I HDACs dual inhibitors |
| title_short | Discovery of novel biphenyl compounds bearing hydroxamic acid moiety as the first PD-L1/class I HDACs dual inhibitors |
| title_sort | discovery of novel biphenyl compounds bearing hydroxamic acid moiety as the first pd l1 class i hdacs dual inhibitors |
| topic | PD-1/PD-L1 HDAC dual inhibitors biphenyl hydroxamic acid |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2025.2461190 |
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