N-イソプロピル-2-[3-[4-[(1H-インダゾール-5-イル)アミノ]キナゾリン-2-イル]フェノキシ]アセトアミド

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説明

Rho-associated protein kinase II (ROCK-II) regulates the formation of actin stress fibers and focal adhesions, smooth muscle contraction, and gene expression. KD 025 is an orally bioavailable inhibitor of ROCK-II that is greater than 200-fold selective over ROCK-I (IC50s = 105 nM and 24 μM, respectively). Treatment of fibrosis-derived smooth muscle cells with KD 025 (40 μM) for 24 hours reduces the expression of connective tissue growth factor and remodels actin cytoskeleton. KD 025 decreases cell-spanning F-actin fibers and increases motility of microvascular endoethelial cells. In mice, KD 025 given by oral gavage dose-dependently reduces infarct volume after transient middle cerebral artery occlusion without causing significant hypotension. In humans, oral KD 025 diminishes STAT3 phosphorylation and pro-inflammatory cytokine production in CD4+ T cells while up-regulating phosphorylation of STAT5 in regulatory T cells, altering the immune response.