Hyunil Jo1, Nilgun I. Reed2 , Yongen Chang2, Dean Sheppard2, William F. DeGrado1,3 1. University of California, San Francisco, Department of Pharmaceutical Chemistry, San Francisco, California, 94158, United States 2. University of California, San Francisco, Lung Biology Center, Department of Medicine, San Francisco, California, 94143, United States 3. University of California, San Francisco, Cardiovascular Research Institute, San Francisco, California, 94158, United States Tissue fibrosis plays a central role in most chronic diseases that lead to organ failure, but there are no currently approved, effective therapies specifically targeting fibrosis in the US. Transforming growth factor β (TGFβ) is a central mediator of fibrotic processes, and its activation thorough av integrins has been increasingly important in therapeutic development. We have developed a potent and highly specific small molecule inhibitor of the αvβ1 integrin and show that this inhibitor completely inhibits TGFβ activation by primary fibroblasts from several organs. We also show that the inhibitor is therapeutically effective in vivo in mouse models of lung, liver and kidney fibrosis. This study suggests that αvβ1 inhibitors may be useful therapeutics for treating fibrotic diseases of multiple organs.

Development of a small molecule inhibitor of integrin αvβ1

249th National Meeting (2015)

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Development of a small molecule inhibitor of integrin αvβ1<br />