LRI-305 (LRI305) is a selective antagonist of Leukemia Inhibitory Factor (LIF) receptor (LIFR), effectively inhibits LIF/LIFR interaction with with IC50 of 0.86 uM in Alpha Screen assays.
LRI-305 reverses the LIF-induced proliferative effects in MKN45 cells with IC50 of 0.7 uM.
LRI-305 exhibits dose-dependent inhibition of STAT3-mediated transcriptional activity with IC50 of 2.9 uM in HepG2 cells transiently transfected with a l STAT3-inducible elements (SIE) luciferase reporter plasmid.
LRI-305 effectively impairs LIF-induced STAT3 signaling and its downstream oncogenic and immunosuppressive effects, including enhanced cell proliferation, EMT, migration, and PD-L1 upregulation in gastric cancer cells.
Combined anti–PD-L1/LRI-305 treatment significantly increased the frequency of double-positive HLA-DR/CD38 activated T cells compared with exposure to conditioned media derived from LIF-treated MKN45 cells alone.