Uses
Z-VAD(OMe)-FMK is a cell-permeable, competitive, and irreversible inhibitor of all caspases. Through this action, it inhibits cleavage of poly(ADP-ribose) polymerase, preventing apoptosis when used at 10-50 μM. It also blocks caspase-mediated apoptosis in vivo. Z-VAD(OMe)-FMK effectively prevents caspase action in inflammasomes.[Cayman Chemical]
Biological Activity
Cell-permeable, irreversible pan-caspase inhibitor. Inhibits caspase processing and apoptosis induction in tumor cells in vitro (IC 50 = 0.0015-5.8 mM). Active in vivo .
Description
Z-VAD-FMK (187389-52-2), cell-permeable, methyl ester form. Potent, irreversible pan-caspase inhibitor. Inhibits caspase activity and apoptosis induction in a variety of cell types (IC50 = 1.5 μM). Active in vivo.
Definition
ChEBI:Z-Val-Ala-Asp(OMe)-CH2F is a tripeptide consisting of Z-Val-Ala-Asp(OMe) in which the C-terminal OH group has been replaced by a fluoromethyl group. An irreversible pan-caspase inhibitor. It has a role as an apoptosis inhibitor and a protease inhibitor. It is a carbamate ester, a tripeptide and an organofluorine compound.
General Description
A cell-permeable, irreversible, pan-caspase inhibitor. Shown to enhance the freeze-thaw survival of human embryonic stem cells. Inhibits Fas-mediated apoptosis in Jurkat T cells. Also reported to inhibit Peptide: N-glycanse (PNGase) in vitro amd in vivo. When using with a purified recombinant enzyme, pretreatment with an esterase is required.
Biochem/physiol Actions
Cell permeable: yes
Enzyme inhibitor
This tripeptide halomethyl ketone (FWfree-acid = 467.49 g/mol; Soluble to
9.35 mg/ml in DMSO; CAS RegistryNumber = 187389-52-2), also known
as Z-VAD-FMK and caspase inhibitor VI, is a broad-spectrum caspase
inhibitor that blocks caspase-mediated apoptosis. Z-VAD-FMK inhibits
caspase processing (IC50 = 0.0015–5.8 mM, depending on enzyme and cell
type). The aspartate methyl ester derivative (FW = 467.49 g/mol), also
known as caspase inhibitor I, is far more cell-permeable. Target (s) :
caspases; caspase-1; caspase-2; caspase-3; caspase-4
; caspase 5; caspase-6; caspase-7; caspase-8 ;
caspase-9; caspase-10.
References
1) Slee et al. (1996), Benzyloxycarbonyl-Val-Ala-ASP (OMe) fluoromethylketone (Z-VAD-FMK) inhibits apoptosis by blocking the processing of CPP32; Biochem. J., 315 21
2) Kunstle et al. (1997), ICE-protease inhibitors block murine liver injury and apoptosis caused by CD95 or by TNF-alpha; Immunol. Lett., 55 5
3) Garcia-Calvo et al. (1998), Inhibition of human caspases by peptide based and macromolecular inhibitors; J. Biol. Chem., 273 32608
