@article{45d401ef749c452f98e72d9b71e3c139,
title = "Development of Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Signaling Pathway",
abstract = "The clinical success of inhibitors targeting the PD-1/PD-L1 pathway has made this an active field in cancer immunotherapy. Currently, most drugs targeting this pathway are monoclonal antibodies. Small-molecule inhibitors as the alternative to monoclonal antibodies are expected to overcome the disadvantages of mAbs which include production difficulties and their long half-life. Recently, progress has been reported on anti-PD-1/PD-L1 small-molecule inhibitors. In this paper, we review the development of inhibitors targeting the PD-1/PD-L1 pathway, focusing mainly on peptide-based and nonpeptidic small-molecule inhibitors. The structures and the preclinical and clinical studies of several peptide-based small-molecule candidate compounds in clinical trials are discussed. We also illustrate the design strategies underlying reported nonpeptidic small-molecule inhibitors and provide insight into possible future exploration. Development of small-molecule drugs for anti-PD-1/PD-L1 activity with specific cancer applications is a promising and challenging prospect.",
author = "Tianyu Wang and Xiaoxing Wu and Changying Guo and Kuojun Zhang and Jinyi Xu and Zheng Li and Sheng Jiang",
note = "Funding Information: This work was supported by the National Natural Science Foundation (Grants 21472191, 81773559), the National Major Scientific and Technological Program for Drug Discovery Grant (Grant 2018ZX09301045002), the International Cooperation Special Grant (Grant 2016A050502036) from the Science and Technology Development Project of Guangdong Province, the International Cooperation Grant (Grant 201704030099) of Guangzhou, and the Science and Technology Planning Project of Guangdong Province (Grant 2013A022100019), and Chinese Pharmaceutical Association-Yiling Biopharmaceutical Innovation Foundation. Funding Information: This work was supported by the National Natural Science Foundation (Grants 21472191, 81773559), the National Major Scientific and Technological Program for Drug Discovery Grant (Grant 2018ZX09301045002), the International Cooperation Special Grant (Grant 2016A050502036) from the Science and Technology Development Project of Guangdong Province, the International Cooperation Grant (Grant 201704030099) of Guangzhou, and the Science and Technology Planning Project of Guangdong Province (Grant 2013A022100019), and Chinese Pharmaceutical Association- Yiling Biopharmaceutical Innovation Foundation. Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",
year = "2019",
month = feb,
day = "28",
doi = "10.1021/acs.jmedchem.8b00990",
language = "English (US)",
volume = "62",
pages = "1715--1730",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "4",
}