Caspase-8 Inhibitor Z-IETD-FMK

Z-IETD-FMK is an inhibitor of caspase 8 [1].

Z-IETD-FMK inhibits T cell proliferation induced by PHA or anti-CD3 plus anti-CD28 without toxicity of resting T cells. The mechanism of this inhibition of Z-IETD-FMK has been proved not through the effect on IL-2 secretion or IFN-γ production but the decrease of CD25 expression. Experiments show that Z-IETD-FMK has no effect on normal cell growth when there is no activation signal. Z-IETD-FMK has also been found to significantly inhibit NF-κB activation when the concentration is 100μM [1].

Apart from the ability of inhibiting cell proliferation, Z-IETD-FMK is reported to inhibit TRAIL-mediated killing in cells. It protects the procaspases 9, 2, and 3, and protects PARP to a similar extent in both HCT116 and SW480 cells [2].

References:
[1] C.P. Lawrence, S.C. Chow. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties. Toxicology and Applied Pharmacology. 2012, 265: 103-112.
[2] Nesrin Özören, Kunhong Kim, Timothy F. Burns, 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 Research. 2000, 60: 6259-6265.