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Small molecule inhibitors of the hedgehog signaling pathway for the treatment of cancer

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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.

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Authors and Affiliations

  1. Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Deajeon, 305-600, Korea

    Jeong In Yun & Hyoung Rae Kim

  2. College of Pharmacy, Chungnam National University, Deajeon, 305-764, Korea

    Jeong In Yun & Sang Kyum Kim

  3. College of Pharmacy, Gangwon National University, Chuncheon, 200-701, Korea

    Haeil Park & Jongkook Lee

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  1. Jeong In Yun
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Yun, J.I., Kim, H.R., Park, H. et al. Small molecule inhibitors of the hedgehog signaling pathway for the treatment of cancer. Arch. Pharm. Res. 35, 1317–1333 (2012). https://doi.org/10.1007/s12272-012-0801-8

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