SPD304 may be used in TNF-α-mediated cell signaling studies.
SPD304 has been used in the inhibition of tumor necrosis factor receptor 1 (TNFR1) in dorsal root ganglion neurons and tumor necrosis factor alpha in colonic epithelial cell lines.
Biochem/physiol Actions
Trimerization of TNF-? is essential for its biological activity. SPD304 inhibits the trimerization by interacting with Glycine 122 residue. It also inhibits the activity of Receptor activator of nuclear factor-?B ligand (RANKL) by similar interaction.
SPD304 is a small molecule inhibitor of TNF-a activity with a novel mechanism of action. It interferes with protein-protein interactions on the contact surfaces of the trimeric TNF-a subunits, displacing one of the trimer units, resulting in dissociation of the trimer and loss of activity at the receptor TNFR1. SPD304 inhibits TNFR1 receptor binding to TNF-a with an IC50 of 22µM in vitro and inhibits TNF-a-mediated stimulation of IkB degradation in HeLa cells with an IC50 of 4.6 µM.