Z-DEVD-FMK

Z-DEVD-FMK is a specific caspase-3 inhibitor with IC50 of 18 uM; affects the survival and function of platelets in platelet concentrate during storage, blocks the geranylgeraniol-induced DNA fragmentation in human leukemia cells; abolishes the apoptosis, CPP32/Mch3alpha processing and the increase in CPP32-like protease activity induced by TGF-beta1 in rat hepatocytes.(In Vitro):N27 cells are exposed to MPP+ in the absence or presence of 50 μM Z-DIPD-FMK or 100 μM Z-DEVD-FMK or 50 μM Z-LEHD-FMK and then caspase-9 and caspase-3 enzymatic activities are determined by enzymatic assay at 12 and 24 h following exposure, respectively. Exposure to 300 μM MPP+ for 24 h in N27 cells results in an approximately 2.5-fold increase in caspase-3 enzyme activity. MPP+-induced increases in caspase-3 enzyme activity are significantly blocked by 50 μM Z-DIPD-FMK, 100 μM Z-DEVD-FMK, and 50 μM Z-LEHD-FMK.(In Vivo):Early Z-DEVD-FMK (160 ng) treatment improves motor and cognitive function after traumatic CNS injury induced by severe controlled cortical impact (CCI) in the mouse. Treatment with Z-DEVD-FMK (160 ng) significantly improves neurological outcome when compared with traumatized animals treated with DMSO vehicle (p<0.01).