TNF-α

Tumor necrosis factor alpha (TNF-α) inhibitors reduce the production or signaling of a central inflammatory cytokine. In 1975 an endotoxin-induced serum factor that causes necrosis of tumors was described and named tumor necrosis factor. Cloning of human TNF in 1984 revealed a precursor related to lymphotoxin. Through its two receptors, TNF-α activates nuclear factor kappa B (NF-κB) and cell death pathways. Etanercept is a soluble receptor fusion protein that binds the cytokine, and C 87 is a small-molecule TNF-α inhibitor. In 1991 thalidomide was shown to inhibit TNF-α production by stimulated human monocytes, and its analogs lenalidomide and pomalidomide are also listed. Pathway compounds include the NF-κB inhibitor QNZ and necrostatin-1, an inhibitor of receptor-interacting protein kinase 1 (RIPK1).