Design, synthesis, and structure--activity-relationship of tetrahydrothiazolopyridine derivatives as potent smoothened antagonists.

The Smoothened (Smo) receptor is an important component of the hedgehog (Hh) signaling pathway, which plays a critical role during embryonic development. In adults, Hh signaling is curtailed and has limited functions such as stem cell maintenance and tissue repair. However, aberrant activity of the Hh signaling in adults has been linked to numerous human cancers.

Scaffold hopping approach to a new series of smoothened antagonists.

The hedgehog (Hh) signaling pathway is a key regulator during embryonic development, while in adults, it has limited functions such as stem cell maintenance and tissue repair. The aberrant activity of the Hh signaling in adults has been linked to numerous human cancers. Inhibition of Hh signaling therefore represents a promising approach toward novel anticancer therapies.