Smoothened Agonist (SAG) HCl is a cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells.
SAG regulates Smo activity by binding directly to the Smo heptahelical bundle. [1] SAG induces Smo-dependent signaling through Gli in a GRK2-dependent way. [2] SAG also (1 nM) induces proliferation of neuronal and glial precursors without affecting the differentiation pattern of newly produced cells. [3]
In the adult rat hippocampus, the intracerebroventricular administration of SAG (2.5 nM) significantly increases the number of newly generated cells and extends survival of hippocampal cells. [3] In mice, SAG (20 μg/g, i.p.) effectively prevents GC-induced neonatal cerebellar developmental abnormalities. [4]
[1] Chen JK, et al. Proc Natl Acad Sci U S A. 2002, 99(22), 14071-14076. [2] Meloni AR, et al. Mol Cell Biol. 2006, 26(20), 7550-760. [3] Bragina O, et al. Neurosci Lett. 2010, 482(2), 81-85.