TNF-TNFR Interaction Modulator, C87

A phenylhydrazonodihydropyrazolone compound that inhibits TNFα/β-stimulated biological activity by modulating, but not abolishing, TNF-TNFR interaction via direct TNF affinity interaction (K_D = 110 nM in binding study using hTNFα). Shown to prevent murine L929 cell death following hTNFα/β (1 ng/mL; Cat. Nos. 654205 & 654215) and actinomycin D (1 g/mL; Cat. Nos. 114666 & 2472-OP) treatment (EC₅₀ = 8.73 M by MTT assay; 20 h TNF/ActD treatment) by blocking TNF/ActD-induced caspase-3/8 cleavages & IκBα degradation without affecting Fas- (CD95) mediated Jurkat cell death or VP-16 (Etoposide; Cat. No. 341205) and ADR (Adriamycin/Doxorubicin; Cat. No. 324380) cytotoxicity in L292 cultures. When applied prior to D-galactosamine (1.2 g D-GalN/kg, Cat. No. 34539) & Lipopolysaccharide (LPS; 50 g/kg) injection, C87 effectively prevents D-GalN/LPS-induced upregulation of plasma alanine transaminase & aspartate transaminase (ALT & AST) activity, resulting in significantly reduced liver damage and much improved survival rate (58.5% vs. 20.8% with or without 3X 12.5 mg C87/kg i.p. dosings 16, 8, & 1 h prior to D-GalN/LPS injection) in a murine hepatitis model in vivo. A slow and long-lasting (>12 h) JNK T183/Y185 phosphorylation is induced upon TNFα stimulation in L929 cultures, while a much faster and more transient, albeit robust, TNFα-induced JNK pT183/Y185 is seen in the presence of C87 or a TNFα neutralizing antibody.

Cell permeable: yes

Primary Target
TNFα

Reversible: yes

Target K_i: 110 nM for hTNF&alpha

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Use only fresh DMSO for reconstitution.

Ma, L., et al. 2014. J. Biol. Chem.289, 12457.

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