Modifying TNFalpha for therapeutic use: a perspective on the TNF receptor system.
TNFalpha is an inflammatory mediator that is relevant to several autoimmune diseases. Macromolecular inhibitors of TNFalpha have proven therapeutically useful in some preliminary studies. We have developed small molecule TNFalpha antagonist based on the crystal structure of TNF receptor complex. The TNFalpha inhibitor is specific and mediates biological function similar to the inhibitory soluble TNF receptor. This review focuses on development of small molecule anti-TNFalpha mimetics by us and current status of other agents.
D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy*; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000627:therapeutic use*; D011487:Protein Conformation; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000737:chemistry
D000893:Anti-Inflammatory Agents; D009842:Oligopeptides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha