480073

MLKL Inhibitor, Necrosulfonamide

MLKL Inhibitor, Necrosulfonamide, CAS 432531-71-0, is a cell-permeable inhibitor that covalently modifies Cys88 and blocks human MLKL adaptor function.

• Synonyme(s) : MLKL Inhibitor, Necrosulfonamide, Necrosis Inhibitor III, Mixed Lineage Kinase Domain-Like Protein Inhibitor, Necrosome Inhibitor II, Necrosulfonamide, (E)-N-(4-(N-(3-Methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide
• Formule empirique (notation de Hill): C₁₈H₁₅N₅O₆S₂
• Numéro CAS: 432531-71-0
• Poids moléculaire : 461.47
• Code UNSPSC : 12352200

Propriétés

• Niveau de qualité: 100
• Pureté: ≥95% (HPLC)
• Forme: solid
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: dark yellow
• Solubilité: DMSO: 100 mg/mL
• Conditions d'expédition: ambient
• Température de stockage: 2-8°C
• InChI: 1S/C18H15N5O6S2/c1-29-18-17(19-10-11-20-18)22-31(27,28)14-6-2-12(3-7-14)21-15(24)8-4-13-5-9-16(30-13)23(25)26/h2-11H,1H3,(H,19,22)(H,21,24)/b8-4+
• Clé InChI: FNPPHVLYVGMZMZ-XBXARRHUSA-N

Description

Description générale

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.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
human MLKL

Reversible: no

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

Use only fresh DMSO for reconstitution.

Autres remarques

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

Informations légales

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

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable