187389-52-2 Usage
Description
Z-VAD-FMK, also known as Z-VAD(OMe)-FMK, is a cell-permeable, irreversible pan-caspase inhibitor. It is a potent compound that effectively inhibits caspase activity and apoptosis induction in a variety of cell types. Z-VAD-FMK is characterized by its ability to block caspase-mediated apoptosis both in vitro and in vivo, making it a valuable tool in the study of apoptosis and related cellular processes.
Uses
Used in Cell Biology Research:
Z-VAD-FMK is used as a research tool for inhibiting apoptosis and caspase processing in various cell types, including Jurkat T cells treated with low concentrations of z-FA-CMK. It helps researchers understand the role of caspases in cell death and survival mechanisms.
Used in Apoptosis Studies:
Z-VAD-FMK is employed as an inhibitor of all caspases, preventing the cleavage of poly(ADP-ribose) polymerase and blocking caspase-mediated apoptosis in vivo. This application aids in the investigation of the molecular mechanisms underlying apoptosis and the potential development of therapeutic strategies targeting caspase activity.
Used in Inflammasome Research:
Z-VAD-FMK is used as an inhibitor to prevent caspase action in inflammasomes, which are multi-protein complexes involved in the activation of inflammatory responses. This application is crucial for understanding the role of caspases in inflammation and the development of anti-inflammatory therapies.
Used in Cryopreservation:
Z-VAD-FMK is used as a cryoprotective agent to enhance the freeze-thaw survival of human embryonic stem cells. By inhibiting caspase activity, it helps maintain cell viability and integrity during the cryopreservation process.
Used in Pharmaceutical Development:
Z-VAD-FMK is used as a lead compound in the development of new drugs targeting caspase-mediated pathways. Its potent and irreversible inhibition of caspases makes it a promising candidate for the treatment of diseases associated with abnormal apoptosis, such as neurodegenerative disorders and certain types of cancer.
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 .
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
Check Digit Verification of cas no
The CAS Registry Mumber 187389-52-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,8,7,3,8 and 9 respectively; the second part has 2 digits, 5 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 187389-52:
(8*1)+(7*8)+(6*7)+(5*3)+(4*8)+(3*9)+(2*5)+(1*2)=192
192 % 10 = 2
So 187389-52-2 is a valid CAS Registry Number.
InChI:InChI=1/C22H30FN3O7/c1-13(2)19(26-22(31)33-12-15-8-6-5-7-9-15)21(30)24-14(3)20(29)25-16(17(27)11-23)10-18(28)32-4/h5-9,13-14,16,19H,10-12H2,1-4H3,(H,24,30)(H,25,29)(H,26,31)/t14-,16-,19-/m0/s1
187389-52-2Relevant articles and documents
An improved method for the incorporation of fluoromethyl ketones into solid phase peptide synthesis techniques
Diffley, John F. X.,Joshi, Dhira,Milligan, Jennifer C.,O'Reilly, Nicola,Papageorgiou, George,Zeisner, Theresa U.
, p. 20457 - 20464 (2021/06/26)
An improved and expedient technique for the synthesis of peptidyl-fluoromethyl ketones is described. The methodology is based on prior coupling of an aspartate fluoromethyl ketone to a linker and mounting it onto resin-bound methylbenzhydrylamine hydrochloride. Subsequently, by utilising standard Fmoc peptide procedures, a number of short Z-protected peptides were synthesised and assessed as possible inhibitors of the main protease from SARS-CoV-2 (3CLpro).
