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.
References:
1. Nyormoi et al (2003) Sequence-based discovery of a synthetic peptide inhibitor of caspase 6. Apoptosis 8 371.
2. Y. Zhang C. Goodyer, Selective and Protracted Apoptosis in Human Primary Neurons Microinjected with Active Caspase-3, -6, -7, and -8. The Journal of Neuroscience, 2000, 20(22):8384–8389
3. Microinjected with Active Caspase-3, -6, -7, and -8 Taimen and Kallajoki (2003) NuMA and nuclear lamins behave differently in Fas-mediated apoptosis. J.Cell Sci.116 571.