Smoothened (Smo), a class Frizzled G protein-coupled receptor (class F GPCR), transduces the Hedgehog (Hh) signal across the cell membrane. The canonical Hh pathway functions through major Hh molecules such as Hh ligands, PTCH, Smo, and GLI, whereas the noncanonical Hh pathway involves the activation of Smo or GLI through other pathways. More importantly, Smo is regulated by a separate transmembrane receptor for Hh ligands called Patched (Ptc). Ptc relieves ptc-mediated repression of the seven-transmembrane (7TM) protein Smo. In addition, The Shh signaling pathway serves as a key component in embryonic development and adult stem cell function. After secretion, Shh binds to its receptor Ptch1, which suppresses the Smo receptor.
Purmorphamine, a Purine-derivative, is a smoothened/Smo receptor agonist. Purmorphamine has osteoinductive activity in multipotent mesenchymal progenitor cells. For example, in human osteoblasts differentiated from bone marrow mesenchymal cells, this compound increases alkaline phosphatase (ALP) activity and bone-like nodule formation. In addition, Purmorphamine also up-regulates the expression of a bone transcription factor, Cbfa1. Moreover, Purmorphamine induces osteogenic differentiation in mouse embryonic fibroblast C3H10T1/2 and pre-osteoblast MC3T3-E1 cell lines. Besides, Purmorphamine has a neuroprotective effect. In hypoxic-ischemic (HI) brain injury in neonatal mice, Purmorphamine produces long-term protection against tissue loss and improves neurobehavioral outcomes. It also increases synaptophysin (Syn) and postsynaptic density (PSD) protein 95 expression in HI-treated mice and attenuates synaptic loss. Furthermore, Purmorphamine treatment up-regulates the expression of Shh pathway mediators.
To sum up, Purmorphamine is a smoothened/Smo receptor agonist, with osteoinductive and neuroprotective activities.
 Márcio M Beloti, et al. Cell Biol Int. 2005 Jul;29(7):537-41.