Small-molecule modulators of tumor immune microenvironment

• Published in: Bioorganic chemistry Vol. 145; p. 107251
• Main Authors: Zhang, Jing, Yu, Jia, Liu, Meijing, Xie, Zhizhong, Lei, Xiaoyong, Yang, Xiaoyan, Huang, Sheng, Deng, Xiangping, Wang, Zhe, Tang, Guotao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2024
• Subjects: Immunosuppressive signals; Small-molecule modulators; Structure–activity relationship; Tumor immunotherapy; Small-molecule modulators; Tumor immunotherapy; Structure–activity relationship; Immunosuppressive signals
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107251

PD-L1, IDO1, and TGF-β immunosuppressive signaling pathways are upregulated in tumor cells. Small-molecule immune modulators are exhibited in the picture. [Display omitted] In recent years, tumor immunotherapy, aimed at increasing the activity of immune cells and reducing immunosuppressive effects, has attracted wide attention. Among them, immune checkpoint blocking (ICB) is the most commonly explored therapeutic approach. All approved immune checkpoint inhibitors (ICIs) are clinically effective monoclonal antibodies (mAbs). Compared with biological agents, small-molecule drugs have many unique advantages in tumor immunotherapy. Therefore, they also play an important role. Immunosuppressive signals such as PD-L1, IDO1, and TGF-β, etc. overexpressed in tumor cells form the tumor immunosuppressive microenvironment. In addition, the efficacy of multi-pathway combined immunotherapy has also been reported and verified. Here, we mainly reviewed the mechanism of tumor immunotherapy, analyzed the research status of small-molecule modulators, and discussed drug candidates' structure–activity relationship (SAR). It provides more opportunities for further research to design more immune small-molecule modulators with novel structures.