Z-IETD-FMK is a selective and cell permeable caspase 8 inhibitor. It also inhibits caspase-10. The bis-methyl ester of Z-IETD-FMK blocked CD95-induced apoptosis.
CAT No: HB00018
CAS No:210344-98-2
Synonyms/Alias:IETD (Modifications: N-terminal benzyloxycarbonyl; C-terminal FMK; Glu-2 = Glu(OMe); Asp-4 = Asp(OMe))
Z-IETD-FMK is a synthetic tetrapeptide inhibitor specifically designed to target and irreversibly inhibit caspase-8, a cysteine protease integral to the initiation of apoptosis via the extrinsic pathway. Characterized by its peptide backbone and a fluoromethyl ketone (FMK) reactive group, this compound is widely utilized in experimental systems to dissect the molecular mechanisms of programmed cell death. Its high selectivity for caspase-8 over other caspases enables researchers to study the distinct roles of this protease in apoptosis, immune signaling, and related cellular processes. Z-IETD-FMK is valued in both basic and applied research settings for its ability to modulate caspase activity with precision, thereby facilitating a deeper understanding of cell fate regulation.
Apoptosis research: As a potent and selective inhibitor of caspase-8, Z-IETD-FMK is extensively employed in studies investigating the molecular pathways underlying apoptosis. By blocking caspase-8 activity, researchers can delineate the contribution of the extrinsic death receptor pathway to programmed cell death in various cell types. This application is particularly relevant in experiments aiming to distinguish between the roles of initiator and executioner caspases, as well as to clarify the sequence of molecular events downstream of death receptor activation. The use of this inhibitor enables precise temporal control over apoptotic signaling, providing valuable mechanistic insights into cell death regulation.
Signal transduction studies: The compound plays a critical role in elucidating the interplay between apoptotic and non-apoptotic signaling pathways. Caspase-8 is known to intersect with multiple cellular processes beyond apoptosis, including necroptosis, inflammation, and immune response modulation. By selectively inhibiting caspase-8, Z-IETD-FMK allows researchers to assess the consequences of caspase blockade on alternative cell fate decisions and cytokine production. This approach is instrumental in dissecting cross-talk between death receptor signaling and other intracellular pathways, thereby advancing the understanding of complex cellular networks.
Drug discovery and screening: Z-IETD-FMK serves as a valuable tool compound in the development and validation of novel caspase inhibitors and modulators. In drug screening assays, it is often used as a reference inhibitor to benchmark the efficacy and selectivity of new chemical entities targeting caspase-8 or related proteases. Its well-characterized inhibitory profile makes it suitable for establishing assay sensitivity, optimizing inhibitor potency, and evaluating off-target effects in biochemical and cell-based formats. The compound's utility in these contexts accelerates the identification of promising candidates for further research.
Cellular and molecular biology: In functional studies, the inhibitor is frequently applied to explore the downstream effects of caspase-8 suppression on cellular morphology, gene expression, and protein cleavage events. By integrating Z-IETD-FMK into experimental protocols, scientists can monitor changes in cell viability, stress responses, and the activation of compensatory pathways. Such investigations contribute to a more comprehensive understanding of the cellular consequences of caspase inhibition, informing the design of future experiments and therapeutic strategies.
Immunology research: Caspase-8 has a pivotal role in modulating immune cell activation, differentiation, and survival. The use of selective inhibitors like Z-IETD-FMK enables immunologists to probe the specific functions of caspase-8 in T cell activation, dendritic cell maturation, and cytokine signaling. By applying this compound in in vitro and ex vivo systems, researchers can dissect the molecular basis of immune regulation and uncover new aspects of immune cell biology, particularly in the context of inflammation and immune-mediated diseases.
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