Approach to discovering novel therapeutic agents for osteoporosis based on integrin receptor blockade

Biopolymers
M ChorevM Rosenblatt

Abstract

On a global scale, osteoporosis is a major and growing public health problem. In the United States, osteoporosis is present in 24 million people (mostly women) and contributes to more than 1.3 million fractures/year. Serious morbidity and mortality result from these fractures. Current therapies for osteoporosis are few, efficacy is limited, and side effects problematic. Fundamental to the pathophysiology of osteoporosis is an imbalance between the tightly coupled processes of bone resorption and bone formation that characterize normal bone remodeling. Our laboratory is engaged in a research effort focused on elucidating the role of the osteoclast integrin in bone resorption, defining the nature of ligand-integrin interactions, and developing antagonists for cell surface adhesion molecules, particularly the alpha v beta 3 vitronectin-like integrin receptor present on the surface of human osteoclasts. Peptides containing the internal arginine-glycine-aspartic acid (RGD) motif have been shown to inhibit osteoclast-mediated bone resorption in vivo. We are now designing more potent and selective inhibitors of bone resorption as a potential new mechanism-based therapeutic approach to osteoporosis based on a novel mechanism. In an eff...Continue Reading

References

Jan 1, 1979·Annual Review of Biochemistry·V Chowdhry, F H Westheimer
Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J K ScottI J Goldstein
Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·F P ReinholtD Heinegård
Jan 1, 1991·The Journal of Clinical Investigation·E Ruoslahti
Oct 1, 1990·The Journal of Cell Biology·M SatoR J Gould
Jan 1, 1987·Methods in Enzymology·R PytelaE Ruoslahti
Feb 17, 1989·JAMA : the Journal of the American Medical Association·N M Resnick, S L Greenspan
Oct 23, 1987·Science·E Ruoslahti, M D Pierschbacher
Jun 1, 1986·Annals of Internal Medicine·S R Cummings, D Black
Jan 1, 1985·Epidemiologic Reviews·S R CummingsK J O'Dowd
May 16, 1973·Journal of the American Chemical Society·R BreslowW Washburn
Jan 1, 1970·British Medical Bulletin·C W Emmens

❮ Previous
Next ❯

Citations

Jan 30, 2002·Bioorganic & Medicinal Chemistry Letters·Andreas KlingThomas Subkowski
May 7, 2002·Bioorganic & Medicinal Chemistry Letters·Udo E W LangeChristian Zechel
Apr 17, 1999·Bioorganic & Medicinal Chemistry Letters·J KatadaY Hayashi
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Krishna KadaveruMartin R Schiller
May 28, 2010·Organic & Biomolecular Chemistry·Karen WrightClaudio Toniolo
Apr 1, 2000·Drug Development and Industrial Pharmacy·Q Yang, G Owusu-Ababio
Oct 3, 2003·Journal of Medicinal Chemistry·Luciana MarinelliHorst Kessler
Jan 14, 2000·Journal of Medicinal Chemistry·D G BattP K Jadhav

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.