title: Hedgehog pathway agonism: therapeutic potential and small-molecule development.
abstract: The Hedgehog (Hh) pathway is a developmental signaling pathway that plays multiple roles during embryonic development and in adult tissues. Constitutive Hh signaling has been linked to the development and progression of several forms of cancer, and the application of small-molecule pathway inhibitors as anticancer chemotherapeutics is well studied and clearly defined. Activation of the Hh pathway as a therapeutic strategy for a variety of degenerative or ischemic disorders has also been proposed; however, the development of small-molecule Hh agonists has received less attention. The goal of this review is to highlight the recent evidence supporting the therapeutic potential of Hh pathway activators and to provide a comprehensive overview of small-molecule pathway agonists.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269 (USA). kyle.hadden@uconn.edu.
authors.forename: M Kyle
authors.initials: MK
authors.lastname: Hadden
mesh_terms: D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology; D005938:Glucocorticoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053823:Hedgehog Proteins / Q000819:agonists / Q000378:metabolism*; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013261:Sterols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005938:Glucocorticoids; D053823:Hedgehog Proteins; D054852:Small Molecule Libraries; D013261:Sterols
keywords: Hedgehog signaling; Smoothened; agonists; neurodegenerative; osteodegenerative