Necrosulfonamide

A cell-permeable acrylamide compound that inhibits human, but not murine, MLKL adaptor function via covalent modification of Cys86 and is more potent than Nec-1 (Cat. No. 480065) in preventing necrotic/necroptotic death in human HT-29 (IC₅₀ = 124 nM and 2 µM, respectively), being ineffective against necrosis/necroptosis in murine L929 or apoptosis in human RIP3-null Panc-1 cells. 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.

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.

Cell permeable: yes

Primary Target
human MLKL

Reversible: no

Packaged under inert gas

Toxicity: Standard Handling (A)

Use only fresh DMSO for reconstitution.

Dunai, Z.A., et al. 2012. PLoS One7, e41945.
Sun, L., et al. 2012. Cell 148, 213.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany