ALFAVBETA3 AND ALFAVBETA6 INTEGRIN ANTAGONISTS AS ANTIFIBROTIC AGENTS

摘要

This invention relates to inhibition of .alpha.v integrins, especially .alpha.v.szlig.3 and .alpha.v.szlig.6 integrins, by specific antagonists, preferably non-peptidic antagonists, related compounds and compounds with comparable specificity, that downregulate fibrogenesis by inhibiting cell migration and production of pro-fibrogenic molecules (e.g., collagens, TIMP- 1) and cytokines (e.g., CTGF) by activated hepatic stellate cells/myofibroblast s, activated epithelia and endothelia. These antagonists alone or in combinatio n with other agents can effectively prevent, mitigate or even reverse development of advanced fibrosis, such as fibrosis/cirrhosis of the liver an d fibrosis of other organs, such as lungs, kidneys, intestine, pancreas, skin and arteries.