Identification and in vivo efficacy of small-molecule antagonists of integrin or alpha(v)beta(3) (the vitronectin receptor)

The integrin alpha(V)beta(3) is thought to play a key role in the initiatio n and/or progression of several human diseases, including osteoporosis, res tenosis following percutaneous transluminal coronary angioplasty (PTCA), rh eumatoid arthritis, cancer and ocular diseases. Antagonism of integrin alph a(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 al pha(V)beta(3) antagonists have been identified, several of which are active in disease models, thereby demonstrating the therapeutic potential of alph a(V)beta(3) antagonism. This review will focus on recent advances in the id entification of small-molecule alpha(V)beta(3) antagonists, with an emphasi s on those studies where small-molecule alpha(V)beta(3) antagonists have be en used in proof-of-concept studies in vivo.