Description
General description
A cell-permeable acrylamide compound that inhibits human, but not murine, MLKL adaptor function via covalent modification of Cys86 through Michael addition and is more potent than the RIP1 inhibitor Nec-1 (Cat. No. 480065) in preventing necrotic/necroptotic death in human HT-29 (IC₅₀ = 124 nM and 2 µM with respective drug against 20 ng/mL TNF-&alpha/100 nM Smac mimetic/20 µM Z-VAD-induced death) and FADD-null Jurkat cultures (80% protection against 200 ng/mL TNF-&alpha-induced death by 0.5 µM NSA or 10 µM Nec-1), being ineffective against blocking necrosis/necroptosis in murine L929 or apoptosis in human RIP3-null Panc-1 cells even at concentrations as high as 5 µM. Unlike Nec-1, which prevents necrosome formation by blocking RIP1-RIP3 interaction, MLKL prevents the MLKL-RIP1-RIP3 necrosome complex from interacting with further downstream effectors.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
human MLKL
Reversible: no
Packaging
Packaged under inert gas
Preparation Note
Use only fresh DMSO for reconstitution.
Other Notes
Dunai, Z.A., et al. 2012. PLoS One7, e41945.
Sun, L., et al. 2012. Cell 148, 213.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)
