Z-VAD(OMe)-FMK 是一种细胞可渗透且不可逆的泛半胱天冬酶抑制剂，当使用浓度为 10-50 μM 时，它会抑制 PARP 的裂解，从而防止细胞凋亡。

Z-VAD(OMe)-FMK is a cell-permeable and irreversible pan-caspase inhibitor. It inhibits cleavage of PARP, preventing apoptosis when used at 10-50 μM.

Z-VAD.FMK was a poor inhibitor of PARP protease activity in cell lysates. Z-VAD.FMK (10 μM) is a potent inhibitor of Fas-induced apoptosis [1]. CPP32 is activated during camptothecin-induced apoptosis, and Z-VAD-fmk blocks all features of apoptosis. However, Z-VAD-fmk is inactive in a cell-free system reconstituted from nuclei of untreated HL60 cells and cytosol from camptothecin-treated cells [2]. z-VAD-FMK suppressed TUNEL and caspase-3 staining in endothelial cells, decreased caspase-3 activation, reduced BBB permeability, relieved vasospasm, abolished brain edema, and improved neurological outcome [3].

LPS (30 mg/kg) was administered intravenously to Institute for Cancer Research mice. Z-VAD.fmk was injected before and after the administration of LPS. The injection of Z-VAD.fmk suppressed the caspase-3 activity in lung tissues and significantly decreased the number of terminal dUTP nick-end labeling-positive cells [4]. Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p.) prior to heat-killed group B streptococcus (i.p.) delayed but did not prevent preterm delivery [5].

The human monocytic tumour cell line, THP.1 and the leukaemic T-cell line, Jurkat (clone E-6) were maintained in RPMI 1640 supplemented with 10% (v/v) heat-inactivated fetal calf serum, 100 units/ml penicillin and 100 μg/ml streptomycin in an atmosphere of 5% CO2 in air at 37 °C. The cells were maintained in logarithmic growth phase by routine passage every 2–3 days. To induce apoptosis in THP.1 cells, 2×10^6 cells/ml were incubated either alone or in the presence of cycloheximide (25 μM) and TLCK (100 μM) as previously described. In order to assess the possible effects of various ICE-like protease inhibitors, THP.1 cells were also pretreated for 1 h with Z-VAD.FMK (10 μM), Ac-DEVD-CHO (20 μM) and Ac-YVAD-CHO (20 μM) before being exposed to the apoptotic stimulus. To induce apoptosis in Jurkat cells, 2×10^6 cells/ml were stimulated with 200 ng/ml anti-human Fas as described previously [1].

Mice used in this study were 5- to 6-week-old (20 to 22 g) ICR males. Mice were injected with 30 mg/kg LPS from E. coli serotype O111:B4 through the tail vein. Z-VAD.fmk was dissolved at 2 mg/ml in 1% dimethyl sulfoxide in sterile saline, and administered to mice by the method of Rodriguez et al. A single intravenous injection of Z-VAD.fmk (0.25 mg) was made 15 minutes before LPS injection, followed by three intravenous injections of Z-VAD.fmk (0.1 mg each) per hour. Control mice were injected with the same volume of 1% DMSO in sterile saline [4].

187389-52-2

C22H30FN3O7

467.494

Z-VAD-FMK;Z-Val-Ala-Asp(OMe)-FMK

Ethanol:<1 mgml
DMSO:93 mg/mL (198.93 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years