title: Identification of iminooxothiazolidines as secreted frizzled related protein-1 inhibitors.
abstract: 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.
authors.affiliation: Chemical Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. shim2@wyeth.com
authors.forename: Mengxiao
authors.initials: M
authors.lastname: Shi
authors.forename: Barbara
authors.initials: B
authors.lastname: Stauffer
authors.forename: Ramesh
authors.initials: R
authors.lastname: Bhat
authors.forename: Julia
authors.initials: J
authors.lastname: Billiard
authors.forename: Helga
authors.initials: H
authors.lastname: Ponce-de-Leon
authors.forename: Laura
authors.initials: L
authors.lastname: Seestaller-Wehr
authors.forename: Shoichi
authors.initials: S
authors.lastname: Fukayama
authors.forename: Annamarie
authors.initials: A
authors.lastname: Mangine
authors.forename: Robert
authors.initials: R
authors.lastname: Moran
authors.forename: Girija
authors.initials: G
authors.lastname: Krishnamurthy
authors.forename: Peter
authors.initials: P
authors.lastname: Bodine
authors.forename: Ariamala
authors.initials: A
authors.lastname: Gopalsamy
mesh_terms: 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
chemical_list: D051157:Frizzled Receptors; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D053245:RANK Ligand; D000099274:Frizzled-Related Proteins