Identification of small molecule activators of BMP signaling

PLoS One. 2013;8(3):e59045. doi: 10.1371/journal.pone.0059045. Epub 2013 Mar 19.


Bone Morphogenetic Proteins (BMPs) are morphogens that play a major role in regulating development and homeostasis. Although BMPs are used for the treatment of bone and kidney disorders, their clinical use is limited due to the supra-physiological doses required for therapeutic efficacy causing severe side effects. Because recombinant BMPs are expensive to produce, small molecule activators of BMP signaling would be a cost-effective alternative with the added benefit of being potentially more easily deliverable. Here, we report our efforts to identify small molecule activators of BMP signaling. We have developed a cell-based assay to monitor BMP signaling by stably transfecting a BMP-responsive human cervical carcinoma cell line (C33A) with a reporter construct in which the expression of luciferase is driven by a multimerized BMP-responsive element from the Id1 promoter. A BMP-responsive clone C33A-2D2 was used to screen a bioactive library containing ∼5,600 small molecules. We identified four small molecules of the family of flavonoids all of which induced luciferase activity in a dose-dependent manner and ventralized zebrafish embryos. Two of the identified compounds induced Smad1, 5 phosphorylation (P-Smad), Id1 and Id2 expression in a dose-dependent manner demonstrating that our assays identified small molecule activators of BMP signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / agonists*
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Line, Tumor
  • Chalcone / pharmacology
  • Drug Discovery*
  • Embryo, Nonmammalian / drug effects
  • Embryonic Development / drug effects
  • Flavones / pharmacology
  • Genes, Reporter
  • High-Throughput Screening Assays
  • Humans
  • Mice
  • Mice, Knockout
  • Myoblasts / cytology
  • Myoblasts / drug effects
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Signal Transduction / drug effects*
  • Small Molecule Libraries*
  • Zebrafish


  • Bone Morphogenetic Proteins
  • Flavones
  • Small Molecule Libraries
  • Chalcone