Cyclopamine-KAAD is a potent, cell-permeable analog of Cyclopamine that specifically inhibits the Hedgehog (Hh) signaling with similar or lower toxicity. Cyclopamine-KAAD binds to SmoA1 and promotes its exit from the endoplasmic reticulum. Cyclopamine-KAAD also suppresses both the ShhNp-induced pathway activity and SmoA1-induced reporter activity.