Definition

An orally available, small molecule inhibitor of the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), with potential immune checkpoint inhibitory, anti-viral and antineoplastic activities. Upon administration, PD-L1 inhibitor GS-4224 specifically targets PD-L1 expressed on tumor cells preventing the binding and subsequent activation of its receptor, programmed cell death 1 (PD-1; PDCD1; CD279; programmed death-1). This reverses T-cell inactivation caused by PD-L1/PD-1 signaling, increases T-cell expansion and enhances the cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response against PD-L1-expressing tumor cells. It may also enhance hepatitis B virus (HBV)-specific CD8+ T-cell function, thereby killing HBV-infected cells. PD-L1, a transmembrane protein expressed on activated T cells, is overexpressed in some cancer types and plays a significant role in immune evasion by tumor cells. It is also upregulated in HBV-positive patients and contributes to immune dysfunction against HBV infection.