Caspase-8 inhibitor - Z-IETD-FMK

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Specific inhibitor of Caspase-8 - InvitroFit™

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1 mg

5 x 1 mg

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Caspase-8 inhibitor

Activation of apoptosis using Z-IETD-FMK
Activation of apoptosis using Z-IETD-FMK

Z-IETD-FMK is a potent small-molecule inhibitor of Caspase-8 (CASP-8) [1,2]. CASP-8 plays a key role in regulated cell death, acting as an initiator of apoptosis but an inhibitor of necroptosis [2-4]. Thus, blockade of CASP-8 is necessary for the induction of necroptosis upon engagement of death receptors.

Learn more Learn more about apoptosis and necroptosis


Mode of action:

The tetrapeptide IETD binds preferentially to the active site of CASP-8 [1,2]. The addition of a benzylocarboxonyl group (Z), O-methyl side chains, and a fluoromethyl ketone (FMK) group enhances Z‑IETD‑FMK cell permeability with no additional cytotoxic effects. Through the blockade of CASP-8, Z‑IETD‑FMK acts as an inducer of necroptosis.

Note: For full induction of necroptosis upon death receptor engagement, deubiquitination of RIPK1 is required. This can be achieved by blocking cIAP, responsible for the ubiquitination of RIPK1, using Smac mimetics such as BV6.


Key features:

  • Potent and selective inhibitor of Caspase-8
  • Suppresses RIPK1-dependent apoptosis
  • Contributes to TNF-α-induced RIPK1-dependent necroptosis 
  • InvitroFit™ grade: each lot is highly pure (≥95%) and functionally tested for necroptosis induction



1. Thornberry N.A. et al., 1997. A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem. 272(29):17907-11.
2. Concha, N.O. & Abdel-Meguid, S.S. 2002. Controlling apoptosis by inhibition of caspases. Curr Med Chem. 9(6):713-26.
3. Barnhart B.C. & Peter M.E. 2003. The TNF receptor 1: a split personality complex. Cell. 114(2):148-150.
4. Bertheloot D. et al., 2021. Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cellular & Molecular Immunology. 18:1106-1121.


Dose-dependent induction of necroptosis
Dose-dependent induction of necroptosis

Z-IETD-FMK contributes to TNF-α-induced RIPK1-dependent necroptosis in a dose-dependent manner. THP1-HMGB1-Lucia™ cells were incubated with recombinant human TNF-α (100 ng/ml), BV6 (cIAP inhibitor, 5 µM), and increasing concentrations of Z-IETD-FMK (caspase-8 inhibitor). After overnight incubation, the level of HMGB1::Lucia released in the supernatant was assessed by measuring the light signal produced using the QUANTI‑Luc™ detection reagent. Data are shown as a percentage (%) of maximal cell death induction.

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CAS number: 210344-98-2

Synonym: Z-Ile-Glu(O-ME)-Thr-Asp(O-Me) fluoromethyl ketone

Working concentration: 1-20 µM for cell culture assays

Solubility: 5 mM (3.27 mg/ml) in DMSO

Formula: C30H43FN4O11

Molecular weight: 654.68 g/mol

Quality control:

  • Purity: ≥95% (UHPLC)
  • The inhibitory activity of the product has been validated using in-house cellular assays with THP1-HMGB1-Lucia™ cells.
  • The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.
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Z-IETD-FMK is available in two quantities: 

  • inh-ietd: 1 mg
  • inh-ietd-5: 5 x 1 mg

 Z-IETD-FMK is shipped at room temperature.

 Upon receipt, store at -20 °C.

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Chemical structure of Z-IETD-FMK:

Chemical structure of Z-IETD-FMK

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