A mechanistic perspective, clinical applications, and phage-display-assisted discovery of TNFα inhibitors

TNFa participates in a variety of physiological processes, but at supra physiological concentrations it has been implicated in the pathology of inflammatory and autoimmune diseases. Therefore, much attention has been devoted to the development of strategies that overcome the effects of aberrant TNFa concentration. Promising strategies include drugs that destabilize the active (trimeric) form of TNFa and antagonists of TNFa receptor type I. Underpinning these strategies is the successful application of phage-display technology to identify anti-TNFa peptides and antibodies. Here, we review the development of inhibitors of the TNFa-TNF receptor system, with particular focus on the phage-display-assisted identification of molecules that interfere with this system by acting as inhibitors of TNFa or by sequestering TNFa away from its receptor.

Automated summary

TNFa plays a crucial role in physiological processes, but excessive levels can contribute to inflammatory and autoimmune diseases. Therefore, researchers have focused on developing strategies to counteract aberrant TNFa concentrations. Promising approaches include destabilizing the active form of TNFa and blocking its interaction with TNFa receptor type I. The use of phage-display technology has been successful in identifying peptides and antibodies that inhibit TNFa activity or prevent its binding to its receptor.