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Description

A cell-permeable imidazolyl-isoxazolamide compound that upregulates beta-catenin-regulated transcription (CRT, Effective conc. 10 - 40 µ,M) by blocking/disrupting beta-catenin and Axin interaction, thereby preventing beta-catenin phosphorylation (Ser33/Ser37/Thr41/Ser45) and proteasomal degradation, without affecting the activities of GSK-3alpha/beta or 18 other kinases (<=8.5% inhibition by 10 µ,M SKL2001). Wnt pathway activation by SKL2001 is shown to effectively promote osteoblastogenesis in both human and murine mesenchymal cultures (10 to 40 µ,M) as well as suppress MDI- (dexamethasone and insulin) stimulated adipogenesis of murine 3T3-L1 preadipocytes (5 to 30 µ,M)., A cell-permeable imidazolyl-isoxazolamide that upregulates beta-catenin-regulated transcription (CRT, 10 - 40 µ,M) by disrupting beta-catenin and Axin interaction, thereby preventing beta-catenin phosphorylation (Ser33/Ser37/Thr41/Ser45) and proteasomal degradation, without affecting the activities of GSK-3alpha/beta or 18 other kinases (<=8.5% inhibition by 10 µ,M SKL2001). Shown to effectively promote osteoblastogenesis in both human and murine mesenchymal cultures (10 to 40 µ,M) as well as suppress MDI- (dexamethasone and insulin) stimulated adipogenesis of murine 3T3-L1 preadipocytes (5 to 30 µ,M).