Z-LEHD-FMK

Z-LEHD-FMK is a selective and irreversible inhibitor of caspase-9, protects against lethal reperfusion injury and attenuates apoptosis. Z-LEHD-FMK exhibits the neuroprotective effect in a rat model of spinal cord trauma[1][2][3].

Research Areas >> Cancer

Signaling Pathways >> Apoptosis >> Caspase

Research Areas >> Neurological Disease

Caspase-9

Z-LEHD-FMK (20 μM; pretreated for 30 min) completely protects HCT116 and 293 cells from TRAIL-induced toxicity[1]. Z-LEHD-FMK (20 μM ; 6 h) protects normal human hepatocytes from TRAIL-induced apoptosis[1]. Apoptosis Analysis[1] Cell Line: SW480, H460, HCT116 and 293 cells Concentration: 20 μM Incubation Time: Pretreated for 30 min Result: Protected HCT116 and 293 cells from TRAIL-induced apoptosis. Western Blot Analysis[1] Cell Line: HCT116, SW480 cells Concentration: 20 μM Incubation Time: 2 h Result: Protected procaspase 3 from cleavage in HCT116 cells but not in SW480 cells, especially at the 16-h time point.

Z-LEHD-FMK (0.8 μmol/kg; i.v. for 7 d) protects neurons, glia, myelin, axons, and intracellular organelles in spinal cord injury (SCI) rats[2]. Animal Model: Male Wistar albino rats (250-350 g) with SCI[2] Dosage: 0.8 μmol/kg Administration: I.v. for 1 or 7 days Result: Decreased the mean apoptotic cell count at 24 hours and 7 days postinjury.

[1]. Ozoren N, et, al. The caspase 9 inhibitor Z-LEHD-FMK protects human liver cells while permitting death of cancer cells exposed to tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res. 2000 Nov 15; 60(22): 6259-65.

[2]. Colak A, et, al. Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury. J Neurosurg Spine. 2005 Mar; 2(3): 327-34.

[3]. Mocanu MM, et, al. Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury. Br J Pharmacol. 2000 May; 130(2): 197-200.