ICB-7 is a high affinity, direct Leukocyte immunoglobulin-like receptor B4 (LILRB4/ILT3) binder with MST Kd of 156 nM, binds D2 domain of ILT3, disrupts the ILT3-SCG2 (Secretogranin II) interaction and inhibits downstream SHP1, SHP2, and STAT3 signaling.
ICB-7 produced concentration-dependent thermal stabilization of ILT3 with EC50 of 289 nM in CETSA assays.
ICB-7 inhibited the ILT3-SCG2 interaction in a concentration-dependent fashion with IC50 of 694 nM in TR-FRET competition assay.
ICB-7 significantly reduced SCG2-driven SHP1 and SHP2 phosphorylation in ILT3-expressing THP-1-derived macrophage-like cells stimulated with SCG2 with IC50 of 302 nM in ELISA assays.
ICB-7 strongly decreased p-STAT3 levels in a concentration-dependent manner with IC50 of 196 nM.
ICB-7 (1-25 uM) reverses SCG2-mediated immunosuppression in colorectal cancer and AML co-culture models.
ICB-7 (25 mg/kg, PO, QD) suppresses CT26 tumor growth and promotes anti-tumor immune activation in vivo.