Butamben derivatives enhance BMP-2-stimulated commitment of C2C12 cells into osteoblasts with induction of voltage-gated potassium channel expression

Bioorg Med Chem Lett. 2011 Dec 15;21(24):7363-6. doi: 10.1016/j.bmcl.2011.10.020. Epub 2011 Oct 13.

Abstract

As the primary step for 'drug repositioning', we evaluated the effect of 2000 drugs and drug candidates on the commitment of bi-potential mesenchymal precursor C2C12 cells into osteoblasts in the presence of bone morphogenetic protein (BMP)-2 and found that butamben enhanced BMP-2-stimulated induction of alkaline phosphatase, a biomarker of osteoblastogenesis. Investigating the underlying mechanism of its anabolic actions, we found anabolic action of its derivative (compound 4) relies on BMP-2 signaling and mRNA induction of BMPs and voltage-gated potassium channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminobenzoic Acid / chemistry
  • 4-Aminobenzoic Acid / pharmacology
  • Alkaline Phosphatase / metabolism
  • Animals
  • Benzocaine / analogs & derivatives*
  • Benzocaine / chemistry
  • Benzocaine / pharmacology
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism*
  • Cell Differentiation / drug effects
  • Cell Line
  • Gene Expression Regulation / drug effects
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Potassium Channels, Voltage-Gated / metabolism*
  • RNA, Messenger / metabolism
  • Signal Transduction
  • para-Aminobenzoates*

Substances

  • Bone Morphogenetic Protein 2
  • Potassium Channels, Voltage-Gated
  • RNA, Messenger
  • para-Aminobenzoates
  • Alkaline Phosphatase
  • butamben
  • 4-Aminobenzoic Acid
  • Benzocaine