Z-LEHD-FMK is a specific and irreversible inhibitor of caspase-9 .
Caspase-9 is an initiator caspase and plays an important role in the mitochondrial death pathway. Caspase-9 is activated during programmed cell death and cleaves procaspase-7 and procaspase-3.
Z-LEHD-FMK is a specific and irreversible caspase-9 inhibitor. In HCT116 human colon cancer cell line and 293 human embryonic kidney cell line, Z-LEHD-FMK inhibited apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). These results suggested that TRAIL induced death through the mitochondrial pathway in some human cells. In a colony assay, Z-LEHD-FMK inhibited the reduction of colony growth of HCT116 induced by TRAIL. In normal human hepatocytes, Z-LEHD-FMK protected cells from TRAIL-induced apoptosis. These results suggested that a combination of Z-LEHD-FMK and TRAIL selectively killed cancer cells while protecting normal liver cells .
In rats with focal ischemia/reperfusion, Z-LEHD-FMK improved neurological outcome by 63% and reduced infarction volume by 49% . In spinal cord trauma rat model, Z-LEHD-FMK reduced apoptotic cell count and protected neurons, myelin, axons, glia and intracellular organelles in the spinal cord .
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