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

Bioorg Med Chem Lett. 2019 Mar 15;29(6):786-790. doi: 10.1016/j.bmcl.2019.01.028. Epub 2019 Jan 24.

Abstract

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.

Keywords: Cancer drug discovery; Fragment-based screening; Immunotherapy; PD-L1 inhibitor; Structure-based design.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / chemistry
  • B7-H1 Antigen / metabolism*
  • Crystallography, X-Ray
  • Humans
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Protein Binding
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Small Molecule Libraries