title: Small molecule inhibitors of the hedgehog signaling pathway for the treatment of cancer.
abstract: Over the past decade, the Hedgehog signaling pathway has attracted considerable interest because the pathway plays important roles in the tumorigenesis of several types of cancer as well as developmental processes. It has also been observed that Hedgehog signaling regulates the proliferation and self-renewal of cancer stem cells. A great number of Hedgehog pathway inhibitors have been discovered through small molecule screens and subsequent medicinal chemistry efforts. Among the inhibitors, several Smo antagonists have reached the clinical trial phase. It has been proved that the inhibition of Hedgehog signaling with Smo antagonists is beneficial to cancer patients with basal cell carcinoma and medulloblastoma. In this review, we provide an overview of Hedgehog pathway inhibitors with focusing on the preclinical and/or clinical efficacy and molecular mechanisms of these inhibitors.
authors.affiliation: Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Deajeon, 305-600, Korea.
authors.forename: Jeong In
authors.initials: JI
authors.lastname: Yun
authors.forename: Hyoung Rae
authors.initials: HR
authors.lastname: Kim
authors.forename: Haeil
authors.initials: H
authors.lastname: Park
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
authors.forename: Jongkook
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D000072086:Smoothened Receptor
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor