Modulation of Wnt signaling through inhibition of secreted frizzled-related protein I (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides: part II.
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.
Moore
William J
WJ
Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, United States. moorew2@wyeth.com
Kern
Jeffrey C
JC
Bhat
Ramesh
R
Bodine
Peter V N
PV
Fukyama
Shoichi
S
Krishnamurthy
Girija
G
Magolda
Ronald L
RL
Pitts
Keith
K
Stauffer
Barb
B
Trybulski
Eugene J
EJ
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
D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D013449:Sulfonamides; D051153:Wnt Proteins; D051176:beta Catenin; D000099274:Frizzled-Related Proteins