ZVAD-FMK

SKU: orb1301152

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Description

Z-VAD(OMe)-FMK is a cell-permeable, irreversible pan-caspase inhibitor that also covalently inhibits the deubiquitinase UCHL1 by targeting its active site. It is widely used in apoptosis and proteostasis research, applicable in both in vitro and in vivo models to study programmed cell death and neurodegenerative pathways.

Research Area

Cell Biology

Images & Validation

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Key Properties

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CAS Number	187389-52-2
MW	467.5
Purity	>98%
Formula	C₂₂H₃₀FN₃O₇
SMILES	COC(=O)C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)C)C(=O)CF
Target	Protease
Solubility	Soluble in DMSO (up to 10 mg/ml).

Bioactivity

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Target IC50	SARS-CoV-2 Mpro:0.59 μM
In Vivo	METHODS: To investigate whether in vivo administration of Z-VAD(OMe)-FMK prevents infection-induced preterm labor, a single intraperitoneal injection of Z-VAD(OMe)-FMK (10 mg/kg) was administered to CD1 mice in which preterm labor was induced by heat-killed group B streptococcus (HK-GBS). RESULTS: Z-VAD(OMe)-FMK pretreatment delayed but did not prevent HK-GBS-induced preterm labor in a pregnant mouse model. METHODS: To prevent LPS-induced acute lung injury, Z-VAD(OMe)-FMK (0.25 mg 15 min before LPS stimulation, 0.1 mg three times per hour) was injected intravenously into ICR mice with LPS-induced apoptosis and acute lung injury. RESULTS: Z-VAD(OMe)-FMK inhibited caspase-3 activity in lung tissues. Z-VAD(OMe)-FMK significantly prolonged the survival of mice. Apoptosis may play an important role in acute lung injury, and thus inhibition of caspase activity may provide a new therapeutic approach for the treatment of this disease. Read more...
In Vitro	METHODS: Human leukemia cells HL60 were treated with Z-VAD(OMe)-FMK (50 µM) and camptothecin (50 M) for 3 h. Cell morphology was observed by electron microscopy. RESULTS: Cells treated with camptothecin exhibited typical apoptotic features including cell shrinkage, chromatin condensation and nuclear fragmentation.Z-VAD(OMe)-FMK combination treatment eliminated the camptothecin-induced apoptotic pattern. Z-VAD(OMe)-FMK alone did not affect cell morphology. METHODS: Cholangiocarcinoma cells KKU100, KKU213A and KKU213B were pretreated with Z-VAD(OMe)-FMK (20 µM) for 1 h, followed by CH-MSCs (0%, 50% and 75%) for 24 h. Apoptosis was detected using Flow Cytometry. RESULTS: Z-VAD(OMe)-FMK pretreatment prevented the apoptosis induced by CH-MSCs. METHODS: Human ovarian teratoma cells PA-1 were treated with Z-VAD(OMe)-FMK (50 μM) and UVB (100 J/m2) for 16 h, and the expression levels of target proteins were detected by Western Blot. RESULTS: Z-VAD(OMe)-FMK eliminated PARP cleavage induced by UVB. Read more...
Cell Research	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 . Read more...
Animal Research	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 . Read more...

Storage & Handling

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Storage	-20°C
Expiration Date	12 months from date of receipt.
Disclaimer	For research use only

Alternative Names

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ZVAD(OMe)-FMK

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Compound Identifiers

PubChem CID

5497174 ↗

Key Properties

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No computed properties available.

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Purity:	>98% (HPLC)
CAS Number:	1135695-98-5
MW:	513.49
Formula:	C₂₆H₂₅F₂N₃O₆

ZVAD-FMK

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