New developments in the discovery of small molecule Hedgehog pathway antagonists.
The Hedgehog (Hh) signaling pathway is crucial for normal embryonic development. Aberrant Hh signaling is implicated in numerous pathologic conditions including proliferative diseases such as cancer. During the past decade, academic and industrial research efforts have resulted in the discovery of a variety of Hh pathway antagonists. This review focuses on the most recent advances in this field with particular emphasis on the medicinal chemistry approaches used to discover these Hh antagonists. While most of the small molecule modulators of the Hh pathway were discovered through screening and subsequent medicinal chemistry, a number of them originated from rational design or natural products.
Tremblay
Martin R
MR
Infinity Pharmaceuticals, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA. martin.tremblay@infi.com
McGovern
Karen
K
Read
Margaret A
MA
Castro
Alfredo C
AC
D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D015398:Signal Transduction; D054852:Small Molecule Libraries
D053823:Hedgehog Proteins; D054852:Small Molecule Libraries