In Vitro: 4-IPP is a specific suicide substrate for MIF that binds covalently and irreversibly to MIF to inhibit its biologic activity. ?4-IPP inhibits RANKL-induced p65 phosphorylation and nuclear translocation by preventing the interaction of MIF with thioredoxin-interacting protein-p65 complexes. ?4-IPP can inhibit receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and potentiate osteoblast-mediated mineralization and bone nodule formation. ?4-IPP (0.5-200μM;24-72 hours) inhibits osteoclastogenesis in a dose-dependent manner. ?4-IPP(5-20μM; 5 days) inhibits RANKL-induced osteoclast differentiation and bone resorption .
In Vivo: 4-IPP (1 mg/kg, 5 mg/kg; every 2 days; for 8 weeks) ameliorates the bone loss associated with estrogen deficiency by reducing osteoclastic activities and enhancing osteoblastic bone formation.