Identification and in vivo efficacy of small-molecule antagonists of integrin or αvβ3 (the vitronectin receptor)

The integrin alpha(V)beta(3) is thought to play a key role in the initiation and/or progression of several human diseases, including osteoporosis, restenosis following percutaneous transluminal coronary angioplasty (PTCA), rheumatoid arthritis, cancer and ocular diseases. Antagonism of integrin alpha(V)beta(3) is therefore expected to provide an approach for the treatment and/or prevention of these diseases. A variety of potent, small-molecule alpha(V)beta(3) antagonists have been identified, several of which are active in disease models, thereby demonstrating the therapeutic potential of alpha(V)beta(3) antagonism. This review will focus on recent advances in the identification of small-molecule alpha(V)beta(3) antagonists, with an emphasis on those studies where small-molecule alpha(V)beta(3) antagonists have been used in proof-of-concept studies in vivo.