2. Academic Validation
  3. Insights into non-peptide small-molecule inhibitors of the PD-1/PD-L1 interaction: Development and perspective

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.
Xia Wu 1,  Yangyang Meng 1,  Lei Liu 1,  Guowei Gong 2,  Haotian Zhang 3,  Yunlei Hou 1,  Chunyang Liu 1,  Di Wu 1,  Mingze Qin 4
Affiliations

Affiliations

  • 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: qinmingze001@126.com.
PMID: 33517226 DOI: 10.1016/j.bmc.2021.116038
Abstract

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.

Keywords

Cancer immunotherapy; Non-peptide small-molecule inhibitors; Rational drug design; The PD-1/PD-L1 blockade.

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