Therapeutic applications of small molecule kinase inhibitors in liver fibrosis

The aberrant activities or overexpression of kinases have been closely linked to the development of many diseases, including liver fibrosis, and kinases have become important therapeutic targets for these diseases. Protein kinases, including tyrosine kinases and serine/threonines protein kinases, and phosphoinositide 3-kinase(PI3K)are involved in the development of liver fibrosis through direct and indirect mechanisms, such as regulating the activation of hepatic stellate cells and intrahepatic angiogenesis. Recent studies have shown that small molecule kinase inhibitors(SMKIs)manifest great potential for treating liver fibrosis by inhibiting cell proliferation and angiogenesis. The present review summarizes the activities of tyrosine kinase, serine/threonine kinase and PI3K in liver fibrosis, as well as the pathway they involved in during the development of liver fibrosis, and the recently reported antifibrotic effects of various SMKIs both on preclinical animal models and on patients with liver fibrosis in clinical trials.