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

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.. Authors: Perry, Evan [Vanderbilt Univ., Nashville, TN (United States)]; Mills, Jonathan J. [Vanderbilt Univ., Nashville, TN (United States)]; Zhao, Bin [Vanderbilt Univ., Nashville, TN (United States)]; Wang, Feng [Vanderbilt Univ., Nashville, TN (United States)]; Sun, Qi [Vanderbilt Univ., Nashville, TN (United States)]. DOE Contract: AC02-06CH11357. Subjects: 60 APPLIED LIFE SCIENCES; Cancer drug discovery; Fragment-based screening; Immunotherapy; PD-L1 inhibitor; Structure-based design