生物活性

• 描述Z-FA-FMK is an irreversible inhibitor of cathepsin B, including cathepsins B and L, and also inhibits DEVDase caspase activity. Preincubation with Z-FA-FMK could dose-dependently inhibit activation of caspase at concentration of 30, 60 and 150μM in HeLa cell extracts. The activity inhibition of caspase 2, 3, 6, 7 and 9 could be observed. Pre-treatment with 100μM Z-FA-fmk for 1h could inhibit the induction of DEVDase activity by stimuli in intact Jurkat cells, but without cytochrome c release. Pre-treatment with Z-FA-fmk at concentration ranging in 10-100μM for 2h dose-dependently inhibited processing and activation of caspase-2, 3, 7 and 9, as well as cleavage of Bid, induced by treatment with 1μM MX2870-1 for 3h. Z-FA-FMK could partially inhibit the activity of mature effector caspases in intact cells at low concentration and prevent the cleavage and activation of effector caspases initiated by caspase 9 correlating with partial inhibition of mature caspase 9 at higher concentrations^[1]. Z-FA-FMK is immunosuppressive in vitro and in vivo. Z-FA-FMK inhibited IL-2-driven T cell proliferation by preventing cells from entering and leaving the cell cycle, and inhibited the IL-2 autocrine system in T lymphocytes at concentration of 100μM. The inhibition of translocation of cellular p65 to the nucleus by z-FA-FMK could be observed in purified T cells costimulated with anti-CD3 and anti-CD28. Z-FA-FMK inhibited the processing of caspase-8 and caspase-3 to their respective subunits in resting T cells stimulated through the Ag receptor but not during Fas-induced apoptosis in proliferating T cells. Administration of 25mg/kg, i.v., increased pneumococcal load in the blood and lungs of MFI mice^[2].
• 作用机制Z-FA-fmk can bind to purified caspase.^[1]

• 动物研究
  剂量	Mice[3] (i.v.): 8 mg/kg
  给药途径	i.v.