Identification of iminooxothiazolidines as secreted frizzled related protein-1 inhibitors.
Secreted frizzled related protein-1 (sFRP-1) inhibitors have the potential to be used for the treatment of osteoporosis or other bone related disorders, since the level of sFRP-1 affects osteoblast apoptosis and proliferation. From high throughput screening, we have identified a class of iminooxothiazolidines as sFRP-1 inhibitors. Structure-activity relationships were established for various regions of the scaffold along with the biochemical characterization of this class to probe selectivity, binding and ex vivo activity.
Shi
Mengxiao
M
Chemical Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. shim2@wyeth.com
Stauffer
Barbara
B
Bhat
Ramesh
R
Billiard
Julia
J
Ponce-de-Leon
Helga
H
Seestaller-Wehr
Laura
L
Fukayama
Shoichi
S
Mangine
Annamarie
A
Moran
Robert
R
Krishnamurthy
Girija
G
Bodine
Peter
P
Gopalsamy
Ariamala
A
D002113:Calcification, Physiologic; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D051157:Frizzled Receptors / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D047908:Intracellular Signaling Peptides and Proteins; D015394:Molecular Structure; D010012:Osteogenesis / Q000502:physiology*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification*; D053245:RANK Ligand; D000099274:Frizzled-Related Proteins
D051157:Frizzled Receptors; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D053245:RANK Ligand; D000099274:Frizzled-Related Proteins