045397
CAS Number
187389-52-2Grade
Highly PurifiedMDL Number
MFCD01074990, MFCD03452883Molecular Formula
C₂₂H₃₀FN₃O₇Molecular Weight
467.49EU Commodity Code
38220090Shipping Temp
RTStorage Temp
-20°CZ-VAD-FMK (Cell permeable)
13: PN: WO2005039629 PAGE: 18 claimed protein; 3: PN: WO0158526 SEQID: 3 claimed sequence; 3: PN: WO2011028611 SEQID: 3 unclaimed protein; Z-VAD(OMe)-FMK; Z-Val-Ala-Asp(OMe)-FMK; N-[(Phenylmethoxy)carbonyl]-L-valyl-N-[(1S)-3-fluoro-1-(2-methoxy-2-oxoethyl)-2-oxopropyl]-L-alaninamide; (5S,8S,11S)-Methyl 11-(2-Fluoroacetyl)-5-isopropyl-8-methyl-3,6,9-trioxo-1-phenyl-2-oxa-4,7,10-triazatridecan-13-oate
Cell-permeable, non-selective broad-spectrum caspase inhibitor. Binds irreversibly to the catalytic site of caspase proteases. The peptide is O-methylated in the P1 position on aspartic acid, providing enhanced stability and increased cell permeability. Inhibits ICE-family protease/caspase processing, leading to apoptosis and autophagy induction. Decreases proteasome activity. Potent inhibitor of caspase-1 activation in NLRP3-induced cells. Used in apoptosis and inflammasome studies.
Synonyms
Z-VAD(OMe)-FMK; Z-Val-Ala-DL-Asp(OMe)-FMK; pan-Caspase Inhibitor
Sequence
Z-Val-Ala-DL-Asp(OMe)-fluoromethylketone
Molecular Formula
C₂₂H₃₀FN₃O₇
Solubility
DMSO, acetonitrile or dimethyl formamide.
Usage
Prepare a 10mM stock solution of the caspase inhibitor in high quality DMSO. Add 2ul of stock solution to 1ml of culture medium containing cells to give 20uM final concentration. Effective final concentrations are estimated to be 5-20uM. If a particular inhibitor is applied at higher concentrations, specificity for an individual caspase or even for the caspase family (>100uM) might be compromised. DMSO concentrations above 0.2% may cause cellular toxicity, thus masking the effect of the caspase inhibitor. For in vivo experiments extending 12 to 48 hours, fresh inhibitor may have to be added (injected) due to inactivation by reaction with cysteine protease.
Appearance
Supplied as a white solid.
Storage and Stability
May be stored at 4°C for short-term only. Stable for 12 months after receipt when stored at -20°C. Keep cool and dry. For maximum recovery of product, centrifuge the original vial prior to removing the cap.
Important Note
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications without the expressed written authorization of United States Biological.
Toxicity and Hazards
All products should be handled by qualified personnel only, trained in laboratory procedures.
Intended for research use only. Not for use in human, therapeutic, or diagnostic applications.
References
1. Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32: E.A. Slee, et al.; Biochem. J. 315, 21 (1996)|2. Different interleukin-1 beta converting enzyme (ICE) family protease requirements for the apoptotic death of T lymphocytes triggered by diverse stimuli: A. Sarin, et al.; J. Exp. Med. 184, 2445 (1996)|3. Processing/activation of at least four interleukin-1beta converting enzyme-like proteases occurs during the execution phase of apoptosis in human monocytic tumor cells: M. MacFarlane, et al.; J. Cell Biol. 137, 469 (1997)|4. Processing/activation of caspases, -3 and -7 and -8 but not caspase-2, in the induction of apoptosis in B-chronic lymphocytic leukemia cells: D. King, et al.; Leukemia 12, 1553 (1998)●|Proteasome activities decrease during dexamethasone-induced apoptosis of thymocytes: J. Beyette, et al.; Biochem. J. 332, 315 (1998)|5. JNK (c-Jun N-terminal kinase) and p38 activation in receptor-mediated and chemically-induced apoptosis of T-cells: differential requirements for caspase activation: M. MacFarlane, et al.; Biochem. J. 348, 93 (2000)|6. Statin-induced proinflammatory response in mitogen-activated peripheral blood mononuclear cells through the activation of caspase-1 and IL-18 secretion in monocytes: W.R. Coward, et al.; J. Immunol. 176, 5284 (2006)|7. Broad-spectrum caspase inhibitors: from myth to reality? D. Chauvier, et al.; Cell Death Differ. 14, 387 (2007)|8. A calpain-like protease inhibits autophagic cell death: D.T. Madden, et al.; Autophagy 3, 519- (2007)|9. Malarial hemozoin is a Nalp3 inflammasome activating danger signal; C. Dostert, et al.; PLoS One 4, e6510 (2009)USBio References
No references available