Z-VAD(OMe)-FMK

SKU: orb1301152

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, Protein Biochemistry

Key Properties

• CAS Number: 187389-52-2
• MW: 467.49
• Purity: 99.44%
• 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: Caspase
• Solubility: DMSO:126.25 mg/mL (270.06 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4.5 mg/mL (9.63 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• 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 prolonge 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 fo the treatment of this disease.
• 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 eliminate 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 prevente 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, an the expression levels of target proteins were detected by Western Blot. Results: Z-VAD(OMe)-FMK eliminated PARP cleavage induced by UVB.
• Cell Research:
  The human monocytic tumour cell line, THP.1 an 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℃he cells were maintained in logarithmic growth phase by routine passage every 2–3 days. To induce apoptosis in THP. Cells, × 0^6 cells mL were incubated either alone or in the presence of cycloheximide (25 μM) and TLCK (100 μM) as previously described. In order to asses the possible effects of various ICE-like protease inhibitors, THP. 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, × 0^6 cells mL were stimulated with 200 ng mL anti-human Fas as described previously.
• 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 throug the tail vein. Z-VAD.fmk was dissolved at 2 mg mL in 1% dimethyl sulfoxide in sterile saline, and administered to mice b 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 wit the same volume of 1% DMSO in sterile saline .

Storage & Handling

• Storage: store at low temperature,keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

Caspase, Inhibitor, inhibit, Pan-caspase, Z VAD(OMe) FMK, ZVAD(OMe)FMK, Z-VAD(OMe)-FMK, Z-VAD-FMK, Z-Val-Ala-Asp(OMe)-FMK

Compound Identifiers

PubChem CID

5497174