Integrin antagonists as therapeutics for inflammatory diseases

Abstract

Integrins are a family of heterodimeric cell surface receptors that mediate adhesion events crucial to cellular migration, proliferation and activation. Although critical to a normal immune response, integrins can also facilitate the progression of many inflammatory and autoimmune disorders. As such, they have attracted the attention of the pharmaceutical industry. Several humanised monoclonal antibodies directed against integrin targets have proven to be successful in clinical trials and have been approved for use in humans. This has not only resulted in effective therapies for patients, but also has provided important proof-of-concept studies for the development of small-molecule antagonists. This review focuses on those integrin subclasses that are being evaluated for their potential role in pulmonary, dermatological, gastrointestinal or rheumatic diseases. These include the alpha4 and beta2 integrins, as well as an emerging group of targets from the collagen-binding family of integrins. Interfering with integrin signalling pathways represents a future area of interest. The rationale for pursuing these targets, as well as the drugs presently under development, are discussed.