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Progress on biphenyl derivatives as PD-1/PD-L1 inhibitors

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Abstract

Cancer immunotherapy has achieved a leap from the laboratory to the clinic, especially for therapeutic applications based on programmed cell death-1 (PD-1) and its ligand (PD-L1) that target tumour immune escape and growth. At present, 13 PD-1/PD-L1 monoclonal antibodies (mAbs) have been approved as PD-1/PD-L1 inhibitors by the United States Food and Drug Administration (FDA). However, inherent limitations of mAbs, including poor bioavailability and immunogenicity, have led researchers to pursue alternatives and develop small-molecule inhibitors with low molecular weight. Biphenyl derivatives are small-molecule inhibitors of PD-1/PD-L1 with advantages of oral bioavailability, high tumour penetration and better pharmacokinetic properties. In this work, we review progress and structure-activity relationship analysis of biphenyl derivatives as PD-1/PD-L1 inhibitors. The conclusions could contribute to the design of PD-1/PD-L1 inhibitor candidates for cancer immunotherapy.

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Acknowledgements

This work was supported by the Postdoctoral Science Foundation of Beijing [2022-ZZ-025].

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YLW and SRW designed the research; SRW performed the collection and analysis of data; SRW and HY drafted the article.

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  1. Faculty of environment and life, Beijing University of Technology, Beijing, 100124, PR China

    Shurong Wang & Hong Yan

  2. Beijing Han Dian Pharmaceutical Co., Ltd, Beijing, 100020, PR China

    Shurong Wang & Yuli Wang

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  2. Yuli Wang
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Wang, S., Wang, Y. & Yan, H. Progress on biphenyl derivatives as PD-1/PD-L1 inhibitors. Med Chem Res 32, 2089–2115 (2023). https://doi.org/10.1007/s00044-023-03127-6

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