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When compared to other caspase inhibitors, Z-DRHD-FMK inhibited caspase 6 activity more effectively than the general caspase inhibitor Z-Val-Ala-Asp (OMe)-fluoromethy ketone (Z-VAD-FMK) or the caspase 6 inhibitor Z-Val-Glu(Ome)-Ile-Asp(OMe)-fluoromethyl ketone (Z-VEID-FMK). However, it was less effective in inhibiting TNFα-induced apoptosis than Z-VAD-FMK or Z-VEID-FMK, presumably because caspase 6 is only one of at least three effector caspases, the others being caspase 3 and 7, that are active during caspase dependent apoptosis. Loss of DNA-binding activity and TNFα-induced apoptosis can be prevented by caspase-6-preferred inhibitor (Z-VEID-FMK)1.

The caspase-6-specific inhibitor Z-VEID- FMK and general caspase inhibitors significantly prevent apoptosis of caspase-6-microinjected neurons2.

Z-VEID-FMK, which inhibits caspase-6, was also able to abolish the cleavage of procaspase-8, although caspase-6 is activated downstream of caspase-8 in Fas-mediated apoptosis3.

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