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• W2985062012 startingPage "111876" @default.
• W2985062012 abstract "Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) is a negative immune checkpoint pathway that inhibit immune responses, and upregulation of this pathway has implications in many malignancies. The search for effective PD-1/PD-L1 inhibitors has been at the forefront of academic and industrial medicinal chemistry, leading to 16 clinical candidates and the launch of six monoclonal antibodies (mAbs) drugs. Despite the unprecedented success achieved, the limitations of mAbs, including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, impelled researchers to turn their attention to the development of peptide-based and non-peptide small-molecule inhibitors as potential alternatives or supplements to mAbs. However, no small-molecule inhibitors have been approved so far, indicating a challenging process of developing marketable small-molecule PD-1/PD-L1 targeted therapeutics. This review will summarize and provide insight into recent advances in the PD-1/PD-L1 pathway, including its structural basis and biology, along with the crystal structures with mAbs, peptides and small molecules. We place great emphasis on design strategies underlying reported small-molecule inhibitors and attempt to provide an outlook at the future of small-molecule PD-1/PD-L1inhibitors." @default.
• W2985062012 created "2019-11-22" @default.
• W2985062012 creator A5068058630 @default.
• W2985062012 creator A5076475204 @default.
• W2985062012 creator A5089849298 @default.
• W2985062012 date "2020-01-01" @default.
• W2985062012 modified "2023-10-12" @default.
• W2985062012 title "Progress in PD-1/PD-L1 pathway inhibitors: From biomacromolecules to small molecules" @default.
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