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

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.

• Authors: Xia Wu, Yangyang Meng, Lei Liu, Guowei Gong, Haotian Zhang, Yunlei Hou, Chunyang Liu, Di Wu, Mingze Qin
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 33 Pg. 116038 (03 01 2021) ISSN: 1464-3391 [Electronic] England
• PMID: 33517226 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• Immune Checkpoint Inhibitors
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Small Molecule Libraries

Topics

• B7-H1 Antigen (antagonists & inhibitors, chemistry)
• Drug Development
• Humans
• Immune Checkpoint Inhibitors (chemistry, pharmacology)
• Molecular Docking Simulation
• Molecular Structure
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, chemistry)
• Protein Binding (drug effects)
• Small Molecule Libraries (chemistry, pharmacology)