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Smoothened Agonist, HCl (SAG), is a highly potent activator of Smo (smoothened). This chlorobenzothiophene compound is a hedgehog pathway agonist that interacts with the heptahelical domain of Smo. SAG is shown to act as an activator at low concentrations, but can inhibit Smo coupling at very high concentrations. The activating effects of SAG will counteract Cyclopamine or Cyclopamine-KAAD inhibition of Smo.