Z-VAD-FMK,187389-52-2,IC-0208463

Z-VAD-FMK (Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone), an ICE-like protease inhibitor, inhibits apoptosis by preventing the processing of CPP32 to its active form. [3]
Z-VAD-FMK is immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. Z-VAD-FMK is capable of inhibiting T cell proliferation induced by anti-CD3 plus anti-CD28 or PHA. Besides, z-VAD-FMK inhibits caspase processing during apoptosis but not during T cell activation. Z-VAD-FMK Inhibits caspase processing and apoptosis induction in tumor cells in vitro (IC50 = 0.0015 - 5.8 mM). [1]
Z-VAD-FMK, can be used to induce necroptosis under certain stimuli. Treatment of mice with Z-VAD-FMK could significantly reduce mortality and alleviate disease after lipopolysaccharide (LPS) challenge. Notably, in LPS-challenged mice, treatment with Z-VAD-FMK could also reduce the percentage of peritoneal macrophages by promoting necroptosis and inhibiting pro-inflammatory responses in macrophages. What’s more, pretreatment with Z-VAD-FMK promoted LPS-induced nitric oxide-mediated necroptosis of bone marrow-derived macrophages (BMDMs), leading to reduced pro-inflammatory cytokine secretion. Interestingly, Z-VAD-FMK treatment promoted the accumulation of myeloid-derived suppressor cells (MDSCs) in a mouse model of endotoxin shock, and this process inhibited LPS-induced pro-inflammatory responses in macrophages. Treatment with Z-VAD-FMK alleviates LPS-induced endotoxic shock by inducing macrophage necroptosis and promoting MDSC-mediated inhibition of macrophage activation. For in vivo experienment, the mice were pretreated or post-treated with Z-VAD-FMK (5, 10, and 20 μg/g of body weight) or vehicle (saline) for 2 h and endotoxic shock was induced by an intraperitoneal injection of LPS (10 μg/g of body weight) and saline was used as control. [2]