Biochem/physiol Actions

Reversible: no

Primary Targethuman MLKL

Cell permeable: yes

General description

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.

Legal Information

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

Other Notes

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

Packaging

25 mg in Glass bottle

Packaged under inert gas

Reconstitution

Use only fresh DMSO for reconstitution.

Warning

Toxicity: Standard Handling (A)