TY - JOUR
T1 - Development of Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Signaling Pathway
AU - Wang, Tianyu
AU - Wu, Xiaoxing
AU - Guo, Changying
AU - Zhang, Kuojun
AU - Xu, Jinyi
AU - Li, Zheng
AU - Jiang, Sheng
PY - 2019/2/28
Y1 - 2019/2/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055059191&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055059191&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.8b00990
DO - 10.1021/acs.jmedchem.8b00990
M3 - Review article
C2 - 30247903
AN - SCOPUS:85055059191
VL - 62
SP - 1715
EP - 1730
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 4
ER -