SAG
Hedgehog pathway activator; Activates Smoothened (SMO)
SAG
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SAG (Smoothened Agonist) is a chlorobenzothiophene-containing compound which acts as an activator of the G protein-coupled receptor Smoothened (SMO, EC₅₀ = 3 nM; Chen et al.) SMO is a component of the Hedgehog signaling pathway, which is translocated to the primary cilium after stimulation of the Patched receptor by Hedgehog family ligands, leading to pathway activation. SAG activates SMO via direct binding to the heptahelical bundle (Kd = 59 nM), stabilizing a specific conformation of SMO in cilia and leading to increased downstream gene expression (Rohatgi et al.). SAG abrogates cyclopamine inhibition of SMO, indicating that it acts downstream of cyclopamine (Frank-Kamenetsky et al.; Chen et al.; Lewis & Krieg).
DIFFERENTIATION
- Improves neuronal differentiation of human induced pluripotent stem cells (Mak et al.).
MAINTENANCE
- Induces proliferation and survival of neuronal and glial precursors in vitro and in vivo (Bragina et al.).
- Prevents glucocorticoid neurotoxicity in Math1-Cre, SmoM2 transgenic mice (Heine et al.).
- Rescues cerebellar size and behavioral phenotypes in the Ts65Dn mouse model of Down Syndrome (Das et al.).
