Z-LEHD-FMK TFA is a specific and irreversible inhibitor of caspase-9, providing protection against detrimental reperfusion injury and moderating apoptosis, with demonstrated neuroprotective potential in a rat model of spinal cord trauma.

Z-LEHD-FMK at a concentration of 20 μM, when pretreated for 30 minutes, effectively shields HCT116 and 293 cells from TRAIL-induced toxicity and apoptosis [1]. Furthermore, this compound, when applied for 6 hours, safeguards normal human hepatocytes against TRAIL-induced apoptosis [1]. Apoptosis analysis indicates that a 20 μM concentration of Z-LEHD-FMK, following a 30-minute pretreatment, results in protection against TRAIL-induced apoptosis specifically in HCT116 and 293 cells [1]. Western blot analysis reveals that, at the same concentration and with a 2-hour incubation, Z-LEHD-FMK prevents the cleavage of procaspase 3 in HCT116 cells, showcasing its protective effect against apoptosis. However, this protective effect is not observed in SW480 cells, particularly notable at the 16-hour time point [1].

Z-LEHD-FMK (0.8 μmol/kg; i.v. for 7 d) demonstrates neuroprotective effects in spinal cord injury (SCI) male Wistar albino rats (250-350 g), protecting neurons, glia, myelin, axons, and intracellular organelles[2]. Intravenously administered at 0.8 μmol/kg for 1 or 7 days, it significantly reduces apoptotic cell count at 24 hours and 7 days post-injury[2].