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NSC 668036 is an inhibitor of the Dishevelled (Dvl) protein PDZ domain (Kd = 240 μM for mouse Dvl1 PDZ domain). NSC 668036 interacts with Dvl PDZ at the same binding site as Dapper and Frizzled, native binding partners in the Wnt signaling pathway. NSC 668036 (180 ng) reduces expression of the Wnt target gene, Siamois, in Xenopus embryos and inhibits the ability of injected Wnt3A to induce formation of a secondary axis. At concentrations greater than 10 μM, NSC 668036 inhibits proliferation of NIH/3T3 fibroblasts, restrains their migration in a scratch assay, and blocks the accelerating effect of TGF-β on fibroblast migration. NSC 668036 (5 mg/kg per day for 14 days) reduces the severity of pulmonary fibrosis in mice by bleomycin . NSC 668036 also blocks the bleomycin-induced pulmonary expression of α-smooth muscle actin (α-SMA), collagen I, TGF-β, and β-catenin by 30-50%.

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