Fragment-based screening of programmed death ligand 1 (PD-L1)

[Display omitted] The PD-1 immune checkpoint pathway is a highly validated target for cancer immunotherapy. Despite the potential advantages of small molecule inhibitors over antibodies, the discovery of small molecule checkpoint inhibitors has lagged behind. To discover small molecule inhibitors of...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2019-03, Vol.29 (6), p.786-790
Main Authors: Perry, Evan, Mills, Jonathan J., Zhao, Bin, Wang, Feng, Sun, Qi, Christov, Plamen P., Tarr, James C., Rietz, Tyson A., Olejniczak, Edward T., Lee, Taekyu, Fesik, Stephen
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
B7-H1 Antigen - antagonists & inhibitors
B7-H1 Antigen - chemistry
B7-H1 Antigen - metabolism
Cancer drug discovery
Crystallography, X-Ray
Fragment-based screening
Humans
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Immunotherapy
PD-L1 inhibitor
Protein Binding
Small Molecule Libraries - chemistry
Small Molecule Libraries - metabolism
Structure-based design
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Summary:[Display omitted] The PD-1 immune checkpoint pathway is a highly validated target for cancer immunotherapy. Despite the potential advantages of small molecule inhibitors over antibodies, the discovery of small molecule checkpoint inhibitors has lagged behind. To discover small molecule inhibitors of the PD-1 pathway, we have utilized a fragment-based approach. Small molecules were identified that bind to PD-L1 and crystal structures of these compounds bound to PD-L1 were obtained.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2019.01.028