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

• Published in: Bioorganic & medicinal chemistry letters Vol. 29; no. 6; pp. 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: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.03.2019; Elsevier
• 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; PD-L1 inhibitor; Fragment-based screening; Structure-based design; Cancer drug discovery; Immunotherapy
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2019.01.028

[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.