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

Arch Pharm Res. 2012 Aug;35(8):1317-33. doi: 10.1007/s12272-012-0801-8. Epub 2012 Sep 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Hedgehog Proteins / antagonists & inhibitors*
  • Hedgehog Proteins / metabolism
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Signal Transduction / drug effects
  • Smoothened Receptor


  • Antineoplastic Agents
  • Hedgehog Proteins
  • Receptors, G-Protein-Coupled
  • SMO protein, human
  • Smoothened Receptor