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| Description | SM04690 is a potent and specific inhibitor of canonical Wnt signaling with an EC50 of 19.5 nM for inhibiting the TCF/LEF reporter. It is ∼150- to 500-fold more potent than the other known Wnt inhibitors across multiple cellular assays. | |
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| Targets |
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| In vitro | Bone-marrow-derived hMSCs (CD29+, CD44+ CD166+ CD105+ CD45-), treated with SM04690, show a dose-dependent decrease in the expression of Wnt pathway genes (ASCL1, LEF1, TCF7L2, TCF7, C-262 MYC and AXIN2). M04690 also inhibits the expression of AXIN2, TCF7 and LEF1 in hMSCs and AXIN2 and LGR5 in IEC6 (intestinal stem cells sensitive to Wnt activation) when the Wnt pathway is selectively activated using either Wnt3a or a GSK3β inhibitor, CHIR-99021. SM04690 has minimal effects on the non-canonical Wnt pathway and the BMP pathway. SM04690 protects chondrocytes from catabolic breakdown in vitro[1]. | |
| In vivo | Intra-articular injection of SM04690 promotes cartilage growth and improves joint health in a rat model of knee osteoarthritis. It decreases cartilage breakdown in vivo[1]. |
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