Small molecule antagonists of the LFA-1/ICAM-1 interaction as potential therapeutic agents

Abstract

The interaction between leukocyte function-associated antigen-1 (LFA-1), a member of β₂ integrin family, and intracellular adhesion molecule-1 (ICAM-1) plays a critical role in mediating cell adhesion, leukocyte transmigration and augmentation of T-cell receptor signalling. Small molecule antagonists of LFA-1/ICAM-1 represent a new therapeutic area for treatment of diseases such as psoriasis, rheumatoid arthritis and ischaemic reperfusion injury. The rapid development of this field is evidenced by the increasing numbers of patents filed and numbers of promising preclinical compounds which have emerged in recent years. Most patents claiming LFA-1/ICAM-1-mediated adhesion inhibitors between January 1999 and April 2001 concerned small molecule inhibitors. This review focuses on the novel composition of matter patents in the area of small molecule LFA-1/ICAM-1 interaction antagonists. The mechanism of action for some molecules that inhibit this set of protein-protein interaction will also be discussed.

• cell adhesion
• β
• 2 integrin
• IDAS
• I domain
• Ig domain mimetic
• integrin activation
• ischaemic reperfusion injury
• ICAM-1
• LFA-1
• lymphocyte transmigration
• Mac-1
• MIDAS
• psoriasis