MTX-3937, a Siglec-9 inhibitor with a dissociation constant (Kd) of 3.15 μM, enhances the function and homeostasis of natural killer (NK) cells. Furthermore, MTX-3937 significantly improves the anti-hepatocellular carcinoma efficacy of NK cell-mediated antitumor activity in vivo.

MTX-3937, at concentrations of 5-20 μM over a 24-hour period, significantly enhances the cytotoxic activities of NK92 cells against K562 cells and HepG2-Luc cells. This compound also increases the production of CD107a, TNF-α, and IFN-γ in NK92 cells and human peripheral NK cells in a dose-dependent manner. Additionally, MTX-3937 inhibits the phosphorylation of Siglec-9 and the downstream phosphatases SHP1 and SHP2.

MTX-3937 administered to NK92 cells (20 μM; 24 hours) significantly suppresses the growth of peritoneal hepatocellular carcinoma xenografts over time. Alone, MTX-3937 shows no effect on tumor growth. In the animal model, 6-week-old NCG mice were injected with HepG2-Luc cells. Dosage involved 20 μM-treated NK92 cells, and the administration was carried out via intravenous injection of NK92 cells. The result was an enhanced inhibition of tumor growth and a substantial extension of overall survival in NCG mice.