Carbohydrate Strengthens the Immunotherapeutic Effect of Small-Molecule PD-L1 Inhibitors
文献类型：期刊论文
| 作者 | Dong, Qian1,2,3; Tong, Mengya3; Yu, Xiaolu3; Wang, Lei3; Ao, Jiwei3; Guan, Dongliang3; Tang, Yubo3; Liu, Junjie3; Long, Li3; Tong, Yongliang3 |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2023-05-25 |
| 卷号 | 66期号:11页码:7179-7204 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.2c01347 |
| 通讯作者 | Gong, Likun(lkgong@cdser.simm.ac.cn) ; Lou, Liguang(lglou@simm.ac.cn) ; Huang, Wei(huangwei@simm.ac.cn) |
| 英文摘要 | PD-1/PD-L1 checkpoint blockade has demonstrated greatsuccess incancer immunotherapy. Small-molecule PD-L1 inhibitors also attractsignificant research interests but remain challenging in the efficacyand safety. Carbohydrate moiety and carbohydrate-binding proteins(lectins) play important roles in immune modulation including antigenrecognition and presenting. Herein, we reported a novel strategy tostrengthen the immunotherapeutic effect of small-molecule PD-L1 inhibitorsby introducing sugar motifs, which may utilize the carbohydrate-mediatedimmune enhancement for cancer treatment. The data revealed that glycosidecompounds containing mannose or N-acetylglucosamineexhibited the best results in IFN-gamma secretion. Moreover, comparedto the nonglycosylated compounds, glycosides C3 and C15 demonstrated significant lower cytotoxicity and effectivein vivo antitumor potency in the CT26 and melanoma B16-F10 tumor modelswith good tolerance. Notably, tumor-infiltrating lymphocyte (TIL)analysis validated increased CD3+, CD4+, CD8+, and granzyme B+ T cellsafter glycoside treatments. This work presents a new concept to improvethe immunotherapy. |
| WOS关键词 | MANNOSE RECEPTOR ; IGG ANTIBODIES ; DRUG ; DERIVATIVES |
| 资助项目 | Natural Science Foundation of China (NSFC)[21877116] ; Natural Science Foundation of China (NSFC)[92153301] ; Natural Science Foundation of China (NSFC)[82003574] ; Shanghai Municipal Science and Technology Major Project ; Hangzhou Innovation and Entrepreneurship Leading Team Project[TD2020005] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:001005913900001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306200]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Gong, Likun; Lou, Liguang; Huang, Wei |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Dong, Qian,Tong, Mengya,Yu, Xiaolu,et al. Carbohydrate Strengthens the Immunotherapeutic Effect of Small-Molecule PD-L1 Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2023,66(11):7179-7204. |
| APA | Dong, Qian.,Tong, Mengya.,Yu, Xiaolu.,Wang, Lei.,Ao, Jiwei.,...&Huang, Wei.(2023).Carbohydrate Strengthens the Immunotherapeutic Effect of Small-Molecule PD-L1 Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,66(11),7179-7204. |
| MLA | Dong, Qian,et al."Carbohydrate Strengthens the Immunotherapeutic Effect of Small-Molecule PD-L1 Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 66.11(2023):7179-7204. |
入库方式： OAI收割
来源：上海药物研究所
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