1. Design, synthesis, and structure-activity relationship of PD-1/PD-L1 inhibitors with a benzo[d]isoxazole scaffold.
- Author
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Huang X, Chen H, Dai X, Xu M, Wang K, and Feng Z
- Subjects
- B7-H1 Antigen metabolism, Dose-Response Relationship, Drug, Humans, Immune Checkpoint Inhibitors chemical synthesis, Immune Checkpoint Inhibitors chemistry, Isoxazoles chemical synthesis, Isoxazoles chemistry, Molecular Docking Simulation, Molecular Structure, Programmed Cell Death 1 Receptor metabolism, Structure-Activity Relationship, B7-H1 Antigen antagonists & inhibitors, Drug Design, Immune Checkpoint Inhibitors pharmacology, Isoxazoles pharmacology, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Abstract
Blocking the programmed cell death protein 1 (PD-1) and programmed death-ligand (PD-L1) interaction has emerged as one of the most promising treatments for cancer immunotherapy. A novel series of compounds bearing a benzo[d]isoxazole scaffold was developed as PD-1/PD-L1 inhibitors, among them, compound P20 exhibited the most potent inhibitory activity, with an IC
50 value of 26.8 nM. The preliminary structure-activity relationship was also investigated. The docking analysis of compound P20 with the PD-L1 dimer complex (PDB ID: 5j89) indicated that compound P20 was bound to the PD-L1 dimer with high affinity. These results suggest that compound P20 is a promising lead compound for the development of inhibitors of the PD-1/PD-L1 interaction., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
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