SAG, 1 mg

From STEMCELL Technologies, this Smoothened Agonist (SAG) is a chlorobenzothiophene-containing compound that acts as an activator of the G protein-coupled receptor Smoothened (SMO), with an EC₅₀ of 3 nM (Chen et al.). SMO is a key component of the Hedgehog signaling pathway; upon stimulation of the Patched receptor by Hedgehog family ligands, SMO is translocated to the primary cilium, leading to pathway activation. SAG binds the heptahelical bundle of SMO with a Kd of 59 nM, stabilizing a specific conformation of SMO in cilia and increasing downstream gene expression (Rohatgi et al.). It also abrogates cyclopamine inhibition of SMO, indicating that it acts downstream of cyclopamine (Frank-Kamenetsky et al.; Chen et al.; Lewis & Krieg).

The compound (CAS Number 912545-86-9) has the molecular formula C₂₈H₂₈ClN₃OS, a molecular weight of 490.1 g/mol, and a purity of ≥ 98%. It is supplied as a crystalline solid and is stable at -20°C as supplied; protect from prolonged exposure to light. Solubility is ≤ 40 mM in DMSO and ≤ 40 mM in absolute ethanol. Stock solutions should be prepared fresh before use, and as a general guide are stored at -20°C in DMSO. The compound has low solubility in aqueous media. For cell culture use, dilute stock solution into culture medium immediately before use, and avoid final DMSO concentration above 0.1% due to potential cell toxicity.

Published applications include: improving neuronal differentiation of human induced pluripotent stem cells (Mak et al.); inducing proliferation and survival of neuronal and glial precursors in vitro and in vivo (Bragina et al.); preventing glucocorticoid neurotoxicity in Math1-Cre, SmoM2 transgenic mice (Heine et al.); and rescuing cerebellar size and behavioral phenotypes in the Ts65Dn mouse model of Down Syndrome (Das et al.).