G721-0282 is an orally active inhibitor of CHI3L1 that reduces the expression of inflammatory proteins and cytokines. It suppresses the activation of the NF-κB signaling pathway, inhibits neuroinflammation, and decreases anxiety-related behaviors. Additionally, G721-0282 significantly curtails the proliferation of osteosarcoma (OS) cells by inhibiting the STAT3 signaling pathway and induces apoptosis in OS cells by upregulating pro-apoptotic protein levels while downregulating anti-apoptotic protein levels. This compound is useful in the study of neuroinflammatory diseases and cancer.

G721-0282 (5-20 μM) effectively inhibits LPS-induced neuroinflammation in BV-2 cells, affecting NO production, pro-inflammatory cytokine expression, and inflammatory protein levels. At 20 μM, it demonstrates anti-inflammatory effects in BV-2 cells through CHI3L1 dependency. G721-0282 (10-50 μM, 24-72 hours) impedes MG63 and U2OS cell proliferation in a dose- and time-dependent manner. Additionally, at concentrations of 0-50 μM for 24 hours, it disrupts the cell cycle and induces apoptosis in MG63 and U2OS cells by modulating apoptotic and anti-apoptotic protein levels. Moreover, G721-0282 (0-50 μM, 12-48 hours) significantly reduces the migration and invasion capabilities of these cells by inhibiting the STAT3 signaling pathway. It also suppresses the colony formation ability of osteosarcoma (OS) cells in soft agar over 2-4 weeks. Finally, G721-0282 (0-50 μM, 24 hours) decreases the levels of MMP2 and MMP9.

G721-0282, administered orally at doses of 2.5 and 5 mg/kg twice weekly for four weeks, significantly reduced anxiety-like behavior induced by chronic unpredictable mild stress (CUMS) and inhibited neuroinflammation in male BALB/c mice. Additionally, G721-0282, when given via intraperitoneal injection at a dose of 18.9 mg/kg twice weekly for 35 days, exhibited notable antitumor activity in male BALB/c athymic nude mice with MG63 tumors.