187389-52-2 Usage
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 academic research and scientific papers
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).
