Recent advance of peptide-based molecules and nonpeptidic small-molecules modulating PD-1/PD-L1 protein-protein interaction or targeting PD-L1 protein degradation.

Abstract

Tumor immunotherapy has made great progress in recent years. In the tumor microenvironment, the binding of PD-1 and its ligand PD-L1 can promote tumor immune escape and tumor survival. Clinical studies have indicated that antibodies blocking PD-1 and PD-L1 have reliable effects on many advanced malignant tumors. However, no small-molecule inhibitors have been approved so far, indicating that the development of marketable small-molecules PD-1/PD-L1 targeted therapy drugs is a challenging process. Small-molecule inhibitors can overcome the limitations of monoclonal antibodies, including poor oral bioavailability, high cost, poor tissue and tumor penetration and long half-life, which prompt researchers to turn their attention to the development of peptide molecules and small-molecule inhibitors modulating PD-1/PD-L1 to overcome some disadvantages of monoclonal antibodies or targeting PD-L1 protein degradation as potential alternatives or supplements. In this review, we will focus on the peptide-based and nonpeptidic molecules against PD-1/PD-L1 base on the structural classification. More importantly, we also focus on the latest research progress of small-molecules mediated PD-L1 degradation mechanism.

• Authors: Chenghao Pan, Haiyan Yang, Yang Lu, Shengquan Hu, Yizhe Wu, Qiaojun He, Xiaowu Dong
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 213 Pg. 113170 (Mar 05 2021) ISSN: 1768-3254 [Electronic] France
• PMID: 33454550 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2021 Elsevier Masson SAS. All rights reserved.

Chemical References

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

Topics

• B7-H1 Antigen (antagonists & inhibitors, metabolism)
• Humans
• Immune Checkpoint Inhibitors (chemical synthesis, chemistry, pharmacology)
• Molecular Structure
• Peptides (chemical synthesis, chemistry, pharmacology)
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, metabolism)
• Protein Binding (drug effects)
• Small Molecule Libraries (chemical synthesis, chemistry, pharmacology)