Insights into non-peptide small-molecule inhibitors of the PD-1/PD-L1 interaction: Development and perspective
- Bioorg Med Chem. 2021 Mar 1:33:116038. doi: 10.1016/j.bmc.2021.116038.
- 1. Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
- 2. Department of Bioengineering, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
- 3. Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
- 4. Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: [email protected].
The development of immune checkpoint inhibitors has become a research hotspot in Cancer Immunotherapy in recent years. Anti-PD-1/PD-L1 monoclonal antibodies (mAbs), such as pembrolizumab and nivolumab have been approved for treating different types of Cancer. Many peptides, peptidomimetics and non-peptide small-molecule inhibitors targeting the PD-1/PD-L1 axis have been published so far. In comparison with mAbs, small-molecule inhibitors have the potential to overcome inherent shortcomings of mAbs, such as poor oral bioavailability, low tumor penetration, and high manufacturing costs. In this article, we mainly review non-peptide small-molecule inhibitors of the PD-1/PD-L1 interaction, their cocrystal structures, docking studies, and biological activities are also included to guide future study. In addition, we propose several strategies for designing more effective small-molecule modulators of the PD-1/PD-L1 pathway.