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 . hh - ag 1.2 is a more potent derivative that is also characterized by chen et al . , who refer to it as sag for ' synthetic hh agonist ' . hh - ag 1.5 is the most potent hh agonist reported , 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   but are not shown here .
small - molecule antagonists of hedgehog - pathway signaling , such as cyclopamine , have been known for some time . 
 now , small - molecule agonists of the hedgehog pathway have also been identified . 
 the finding that both antagonists and agonists target the protein smoothened supports the emerging hypothesis that smoothened may be regulated by endogenous small molecules .