Targeting of Smoothened for therapeutic gain.
The Smoothened (Smo) receptor is a key transducer of the Hedgehog (Hh) signaling pathway, which plays a critical role in tissue maintenance and repair. Recent studies have highlighted the therapeutic value of Smo antagonists for treating Hh-linked cancers. Research on Smo agonists indicates that these molecules are important not only for delineating canonical versus noncanonical Hh signaling but also for understanding the role of Smo in physiological and pathological conditions. This review provides an update on the potential therapeutic importance of Smo modulators, and unravels the increasing complexity of its pharmacology with regard to clinical implications.
CNRS, Alfred Fessard Institute of Neurobiology, Laboratory of Neurobiology and Development, UPR-3294, Signal Transduction and Developmental Neuropharmacology Team, Bâtiment 33, 1 avenue de la Terrasse, F-91198 Gif-sur-Yvette, France. Electronic address: ruat@inaf.cnrs-gif.fr.
Martial
M
Ruat
CNRS, Alfred Fessard Institute of Neurobiology, Laboratory of Neurobiology and Development, UPR-3294, Signal Transduction and Developmental Neuropharmacology Team, Bâtiment 33, 1 avenue de la Terrasse, F-91198 Gif-sur-Yvette, France.
Lucile
L
Hoch
CNRS, Alfred Fessard Institute of Neurobiology, Laboratory of Neurobiology and Development, UPR-3294, Signal Transduction and Developmental Neuropharmacology Team, Bâtiment 33, 1 avenue de la Terrasse, F-91198 Gif-sur-Yvette, France.
Hélène
H
Faure
Laboratoire d'Innovation Thérapeutique, UMR 7200, MEDALIS Drug Discovery Center, 74 route du Rhin, 67400 Illkirch, France.
Didier
D
Rognan
D000818:Animals; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor
D053823:Hedgehog Proteins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; C491022:Smo protein, mouse; D000072086:Smoothened Receptor
Hedgehog; bias agonism; cancer; neurodegenerative disease; stem cell