JNU-0921 is a specfiic, small molecule CD137 (4-1BB/TNFRSF9) agonist with EC50 of 64 nM in cell-based luciferase assays, activates both human and mouse CD137, directly binds the extracellular domain of CD137, induces CD137 oligomerizationand activates CD137 signaling.
JNU-0921 treatment stimulated transcription levels of IFN-γ and Granzyme B (GZMB) in JC-luc cells.
JNU-0921 treatment promoted the proliferation of both CD8+ and CD4+ splenic T cells from WT mice in a similar manner to agonistic anti-CD137 antibody (aCD137), but not enhance proliferation of CD137 knockout (KO) T cells.
JNU-0921 treatment increased the levels of CD25 and CD69 in a CD137-dependent manner, up-regulated the expression of effector cytokines in both CD8+ and CD4+ T cells, including IL-2 and IFN-γ.
JNU-0921 promoted the proliferation of CD8+ T cells and CD4+ T cells in human peripheral blood cells.
JNU-0921 binding to CD137 led to recruitment of TRAF2 and TRAF3 to form signaling complex, activates the NF-κB signaling pathway.
JNU-0921 (50 mg/kg per day, gavage) effectively shrinks tumors and rewires tumor immune microenvironment in MC38 xenograft mouse model.