GL-4512 a potent, small molecule direct modulator of leukocyte immunoglobulin-like receptor B4 (LILRB4, ILT3/CD85k) with SPR KD of 39.2 nM for binding to immobilized LILRB4 protein, inhibits LILRB4-SCG2 interaction with IC50 of 37 nM in TR-FRET assays, inhibits LILRB4-mediated immunosup pressive signaling pathways relevant to tumor immune evasion.
GL-4512 demonstrates cellular engagement of LILRB4 with EC50 of 53 nM,
GL-4512 shows direct binding to recombinant human LILRB4 extracellular do main protein with MST KD of 18.1 nM.
GL-4512 attenuated SCG2-induced phosphorylation of both SHP1 and SHP2 with IC50 values of 101 nM and 141 nM in LILRB4-expressing THP-1 derived macrophage-like cells respectively.
GL-4512 markedly suppressed p-STAT3 levels in a dose-de pendent manner (IC50 = 76.3 nM) in SCG2 stimulation induced substantial phosphorylation of STAT3 in LILRB4-expressing cells.
GL-4512 restores anti-tumor immune function across colorectal cancer and AML co-culture systems.
GL-4512 demonstrates cross-species LILRB4 engagement (KD=32.5 nM, recombinant murine LILRB4) and suppresses CT26 tumor progression in vivo (20 mg/kg by oral gavage once daily for 21 days).