title: Modulation of Wnt signaling through inhibition of secreted frizzled-related protein I (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides: part II.
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.
authors.affiliation: Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, United States. moorew2@wyeth.com
authors.forename: William J
authors.initials: WJ
authors.lastname: Moore
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Kern
authors.forename: Ramesh
authors.initials: R
authors.lastname: Bhat
authors.forename: Peter V N
authors.initials: PV
authors.lastname: Bodine
authors.forename: Shoichi
authors.initials: S
authors.lastname: Fukyama
authors.forename: Girija
authors.initials: G
authors.lastname: Krishnamurthy
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Magolda
authors.forename: Keith
authors.initials: K
authors.lastname: Pitts
authors.forename: Barb
authors.initials: B
authors.lastname: Stauffer
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Trybulski
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009924:Organ Culture Techniques; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D012886:Skull / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D000099274:Frizzled-Related Proteins
chemical_list: D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D013449:Sulfonamides; D051153:Wnt Proteins; D051176:beta Catenin; D000099274:Frizzled-Related Proteins