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Z-IETD-FMK

Z-IETD-FMK is a cell-permeable, irreversible caspase-8 inhibitor. It is widely used in cell apoptosis studies. Caspase-8 is a member of the cysteine proteases, which are implicated in apoptosis and cytokine processing. Like all caspases, caspase-8 is synthesized as an inactive single polypeptide chain zymogen procaspase and is activated by proteolytic cleavage, through either autoactivation after recruitment into a multimeric complex or trans-cleavage by other caspases. Thus, ligand binding-induced trimerization of death receptors results in recruitment of the receptor-specific adapter protein Fas-associated death domain (FADD), which then recruits caspase-8. Activated caspase-8 is known to propagate the apoptotic signal either by directly cleaving and activating downstream caspases or by cleaving the BH3 Bcl2-interacting protein, which leads to the release of cytochrome c from mitochondria, triggering activation of caspase-9 in a complex with dATP and Apaf-1. Activated caspase-9 then activates further "downstream caspases," including caspase-8. Knockout data indicate that caspase-8 is required for killing induced by the death receptors Fas, tumor necrosis factor receptor 1, and death receptor 3. Moreover, caspase-8-/- mice die in utero as a result of defective development of heart muscle and display fewer hematopoietic progenitor cells, suggesting that the FADD/caspase-8 pathway is absolutely required for growth and development of specific cell types.

References

View all 27 references: Citation Explorer
Role of caspases in CD95-induced biphasic activation of acid sphingomyelinase.
Authors: Stephan, Mario and Edelmann, Bärbel and Winoto-Morbach, Supandi and Janssen, Ottmar and Bertsch, Uwe and Perrotta, Cristiana and Schütze, Stefan and Fritsch, Jürgen
Journal: Oncotarget (2017): 20067-20085
Caspase-8 inhibition represses initial human monocyte activation in septic shock model.
Authors: Oliva-Martin, Maria Jose and Sanchez-Abarca, Luis Ignacio and Rodhe, Johanna and Carrillo-Jimenez, Alejandro and Vlachos, Pinelopi and Herrera, Antonio Jose and Garcia-Quintanilla, Albert and Caballero-Velazquez, Teresa and Perez-Simon, Jose Antonio and Joseph, Bertrand and Venero, Jose Luis
Journal: Oncotarget (2016): 37456-37470
Caspase blockade induces RIP3-mediated programmed necrosis in Toll-like receptor-activated microglia.
Authors: Kim, S J and Li, Jianrong
Journal: Cell death & disease (2013): e716
Cytokeratin 18 expression inhibits cytokine-induced death of cervical cancer cells.
Authors: Sullivan, Brian T and Cherry, Jessica A and Sakamoto, Hideo and Henkes, Luiz E and Townson, David H and Rueda, Bo R
Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (2010): 1474-81
Non-canonical role for the TRAIL receptor DR5/FADD/caspase pathway in the regulation of MyoD expression and skeletal myoblast differentiation.
Authors: Freer-Prokop, Margot and O'Flaherty, John and Ross, Jason A and Weyman, Crystal M
Journal: Differentiation; research in biological diversity (2009): 205-12
Page updated on October 30, 2024

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Catalog Number13305
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Physical properties

Molecular weight

654.69

Solvent

DMSO

Storage, safety and handling

H-phraseH303, H313, H333
Hazard symbolXN
Intended useResearch Use Only (RUO)
R-phraseR20, R21, R22

Storage

Freeze (< -15 °C); Minimize light exposure
UNSPSC12171501