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

Bioorg Med Chem. 2010 Jan 1;18(1):190-201. doi: 10.1016/j.bmc.2009.11.002. Epub 2009 Nov 6.

Abstract

Piperidinyl diphenylsulfonyl sulfonamides are a novel class of molecules that have inhibitory binding affinity for sFRP-1. As a secreted protein sFRP-1 inhibits the function of the secreted Wnt glycoprotein. Therefore, as inhibitors of sFRP-1 these small molecules facilitate the Wnt/beta-catenin canonical signaling pathway. Details of the structure-activity relationships and biological activity of this structural class of compounds will be discussed.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Glycoproteins / antagonists & inhibitors*
  • Glycoproteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Microsomes, Liver / metabolism
  • Organ Culture Techniques
  • Osteogenesis / drug effects
  • Rats
  • Signal Transduction / drug effects*
  • Skull / cytology
  • Skull / drug effects
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism

Substances

  • Glycoproteins
  • Intracellular Signaling Peptides and Proteins
  • Sulfonamides
  • WD repeat containing planar cell polarity effector
  • Wnt Proteins
  • beta Catenin