Modifying TNF alpha for Therapeutic Use  A Perspective on the TNF Receptor System

Akihiro      Hasegawa; Watrau      Takasaki; Mark   I.   Greene; Ramachandran      Murali

Abstract

TNF alpha is an inflammatory mediator that is relevant to several autoimmune diseases. Macromolecular inhibitors of TNF alpha have proven therapeutically useful in some preliminary studies. We have developed small molecule TNF alpha antagonist based on the crystal structure of TNF receptor complex. The TNF alpha inhibitor is specific and mediates biological function similar to the inhibitory soluble TNF receptor. This review focuses on development of small molecule anti-TNF alpha mimetics by us and current status of other agents.

Keywords: Modifying TNF, inflammatory mediator, TNF receptor, transplantable tumors, destructive arthritis, CDR loops, Neutralizing antibodies, constraining cysteine residues, peptidomimetics, Cyclic peptides, EAE conditions