Figure 1.

The structures of small molecules that activate or inhibit Hedgehog (Hh) signaling. (a) The leiosamine family of compounds that activate Hh signaling by binding to Smoothened. Hh-Ag (Hedgehog agonist) 1.1 was the original compound identified in the high-throughput screen by Frank-Kamenetsky et al.[9], with an EC₅₀ of 3 μM in their luciferase reporter assay. Hh-Ag 1.2 is a more potent derivative that is also characterized by Chen et al.[17], who refer to it as SAG for 'synthetic Hh agonist'. Hh-Ag 1.5 is the most potent Hh agonist reported [9], with an E₅₀ of 1 nM. (b) The structures of two compounds that bind to Smoothened to inhibit Hh signaling, cyclopamine and Cur61414. Structurally distinct classes of Smoothened antagonists have also been reported [17] but are not shown here.