| 摘要 |
Methods and compositions of inhibitors of MAPK kinases 1 and 2 (MEK1 and MEK2, or together, MEK1/2), such as ARRY142886, and their use in inhibiting MEK1/2 kinase activity in mammals for the treatment and/or reversal of the symptoms of pulmonary fibrosis. MEK1/2 inhibitors can selectively inhibit the MAPK/ERK pathway in vivo and prevent TGF-α mediated fibrosis. There are several distinct MAPK pathways that are important in the regulation of cell proliferation, differentiation, development, inflammation, survival, and migration. The Ras-Raf-MEK-ERK pathway (a key component of the MAPK pathway) via inhibition of MEK1/2 is an attractive strategy for therapeutic intervention in idiopathic pulmonary fibrosis, because inhibition of MEK1/2 has the potential to block inappropriate signal transduction leading to pulmonary fibrosis, regardless of the upstream position of the aberration causing it. |
