Modulation of Wnt signaling through inhibition of secreted frizzled-related protein I (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides

J Med Chem. 2009 Jan 8;52(1):105-16. doi: 10.1021/jm801144h.

Abstract

The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or other bone-related disorders. Details of the structure-activity relationships and biological activity from the first structural class of this scaffold will be discussed.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Genes, Reporter / genetics
  • Humans
  • Inhibitory Concentration 50
  • Intracellular Signaling Peptides and Proteins
  • Isomerism
  • Mice
  • Molecular Structure
  • Piperidines / chemistry*
  • Protein Binding
  • Proteins / antagonists & inhibitors*
  • Proteins / metabolism*
  • Signal Transduction / drug effects*
  • Skull / drug effects
  • Structure-Activity Relationship
  • Sulfanilamides / chemical synthesis*
  • Sulfanilamides / chemistry
  • Sulfanilamides / pharmacology*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Piperidines
  • Proteins
  • Sulfanilamides
  • WD repeat containing planar cell polarity effector
  • Wnt Proteins
  • piperidine