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Chemical Structure| 187389-52-2 Chemical Structure| 187389-52-2

Structure of Z-VAD(OMe)-FMK
CAS No.: 187389-52-2

Chemical Structure| 187389-52-2

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Z-VAD(OMe)-FMK is a cell-permeable, irreversible broad-spectrum caspase inhibitor, blocks all features of apoptosis.

Synonyms: Z-Val-Ala-Asp(OMe)-FMK; Z-Val-Ala-Asp-(OMe)-Fluoromethyl Ketone; Z-VAD-FMK

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Product Citations

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Rathje, Oliver H. ; Perryman, Lara ; Payne, Richard J. ; Hamprecht, Dieter W. ;

Abstract: Mixed Lineage Kinase domain-Like pseudokinase (MLKL) is implicated in a broad range of diseases due to its role as the ultimate effector of necroptosis and has therefore emerged as an attractive drug target. Here, we describe the development of PROteolysis TArgeting Chimeras (PROTACs) as a novel approach to knock down MLKL through chem. means. A series of candidate degraders were synthesized from a high-affinity pyrazole carboxamide-based MLKL ligand leading to the identification of a PROTAC mol. that effectively degraded MLKL and completely abrogated cell death in a TSZ model of necroptosis. By leveraging the innate ability of these PROTACs to degrade MLKL in a dose-dependent manner, the quant. relationship between MLKL levels and necroptosis was interrogated. This work demonstrates the feasibility of targeting MLKL using a PROTAC approach and provides a powerful tool to further our understanding of the role of MLKL within the necroptotic pathway.

Yang, Yang ; Wang, Qi ; Song, Dongjian ; Zen, Ruirui ; Zhang, Lei ; Wang, Yingjun , et al.

Abstract: Background: Autophagy is an intracellular process through which intracellular components are recycled in response to nutrient or growth factor deficiency to maintain homeostasis. We identified the peptide autophagy-related cancer-suppressing peptide (ARCSP), a potential antitumor peptide that disrupts intracellular homeostasis by blocking autophagic flux and causes cytotoxic death. Methods: The proliferative ability of ARCSP-treated cervical cancer cells was examined by the CCK8, EdU, and colony formation assays. The TUNEL assay was used to detect apoptosis. Mitochondrial function was evaluated based on the mitochondrial membrane potential. Autophagic flux was detected by immunofluorescence and confocal microscopy. The autophagy-related proteins AMPK, Raptor, mTOR, p62, LC3B, atg7, Rab7, LAMP1, LAMP2, and cathepsin D were detected by Immunoblotting. The antitumor effect of ARCSP was explored in vivo by establishing a transplant tumor model in nude mice. Results: The results demonstrated that ARCSP induced cell death and inhibited proliferation. ARCSP induced AMPK/mTOR activation, resulting in the accumulation of the proteins LC3B, p62 and Atg7. ARCSP also blocked autophagosome-lysosome fusion by inhibiting endosomal maturation and increasing the lysosomal pH. The accumulation of nonfused autophagosomes exacerbated cytotoxic death, whereas knocking down Atg7 reversed the cytotoxic death induced by ARCSP. ARCSP-treated cells exhibited increased cytotoxic death after cotreatment with an autophagy inhibitor (Chloroquine CQ). Furthermore, the tumors of ARCSP-treated nude mice were significantly smaller than those of untreated mice. Conclusions: Our findings demonstrate that ARCSP, a novel lethal nonfused autophagosome inducer, might cause mitochondrial dysfunction and autophagy-related cytotoxic death and is thus a prospective agent for cancer therapy.

Keywords: Cervical cancer ; ARCSP ; Autophagic flux ; Nonfused autophagosome ; Autophagy-related cytotoxic death

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Product Details of Z-VAD(OMe)-FMK

CAS No. :187389-52-2
Formula : C22H30FN3O7
M.W : 467.49
SMILES Code : COC(C[C@@H](C(CF)=O)NC([C@@H](NC([C@@H](NC(OCC1=CC=CC=C1)=O)C(C)C)=O)C)=O)=O
Synonyms :
Z-Val-Ala-Asp(OMe)-FMK; Z-Val-Ala-Asp-(OMe)-Fluoromethyl Ketone; Z-VAD-FMK
MDL No. :MFCD02684037
InChI Key :MIFGOLAMNLSLGH-QOKNQOGYSA-N
Pubchem ID :5497174

Safety of Z-VAD(OMe)-FMK

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Z-VAD(OMe)-FMK

pyroptosis

Isoform Comparison

Biological Activity

Target
  • Caspase

In Vitro:

Cell Line
Concentration Treated Time Description References
KG-1a cells 50 µM 48 h partially prevented the apoptotic cell death induced by emetine Cell Death Discov. 2024 Apr 29;10(1):201.
KG-1a cells 50 µM 2 h Pretreatment with Z-VAD(OMe)-FMK significantly reduced PL-induced apoptosis in KG-1a cells, indicating that PL induces apoptosis through a caspase-dependent pathway. Cell Death Discov. 2024 Mar 19;10(1):147.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.14mL

0.43mL

0.21mL

10.70mL

2.14mL

1.07mL

21.39mL

4.28mL

2.14mL

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