Small molecules that promote osteoblast differentiation might be useful as therapeutic agents for bone diseases such as osteoporosis. Purmorphamine is a 2,6,9-trisubstituted purine that promotes the differentiation of both human and mouse mesenchymal progenitor cells into osteoblasts.1,2 The EC50 value for differentiation of C3H10T1/2 cells based on alkaline phosphatase expression is 1 µM.1 Investigation into purmorphamine’s mechanism of action indicates that it directly binds to and activates the 7-transmembrane Smo receptor of the Hedgehog signaling pathway.3,4
1Wu, X., Ding, Q., Gray, N.S., et al. A small molecule with osteogenesis-inducing activity in multipotent mesenchymal progenitor cells. J Am Chem Soc12414520-14521(2002).
2Beloti, M.M., Bellesini, L.S., and Rosa, A.L.Purmorphamine enhances osteogenic activity of human osteoblasts derived from bone marrow mesenchymal cells. Cell Biol Int29(7)537-541(2005).
3Wu, X., Walker, J., Zhang, J., et al. Purmorphamine induces osteogenesis by activation of the hedgehog signaling pathway. Chem Biol111229-1238(2004).
4Sinha, S., and Chen, J.K.Purmorphamine activates the hedgehog pathway by targeting smoothened. Nat Chem Biol2(1)29-30(2006).
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