Purmorphamine activates the Hedgehog pathway by targeting Smoothened

Nat Chem Biol. 2006 Jan;2(1):29-30. doi: 10.1038/nchembio753. Epub 2005 Nov 20.

Abstract

Hedgehog (Hh) signaling is an important regulator of embryonic patterning, tissue regeneration, stem cell renewal and cancer growth. A purine derivative named purmorphamine was previously found to activate the Hh pathway and affect osteoblast differentiation through an unknown mechanism. We demonstrate here that purmorphamine directly targets Smoothened, a critical component of the Hh signaling pathway.

Publication types

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

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Hedgehog Proteins
  • Mice
  • Morpholines / pharmacology*
  • NIH 3T3 Cells
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Purines / pharmacology*
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Smoothened Receptor
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Tissue Engineering
  • Trans-Activators / metabolism*
  • Veratrum Alkaloids / pharmacology

Substances

  • Hedgehog Proteins
  • Morpholines
  • Purines
  • Receptors, G-Protein-Coupled
  • Smo protein, mouse
  • Smoothened Receptor
  • Trans-Activators
  • Veratrum Alkaloids
  • purmorphamine
  • cyclopamine

Associated data

  • PubChem-Substance/7851482
  • PubChem-Substance/7851483
  • PubChem-Substance/7851484
  • PubChem-Substance/7851485
  • PubChem-Substance/7851486