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A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
Published on: June 9, 2014
alpha(v)beta(3) Integrin antagonists as inhibitors of bone resorption
1Department of Medicinal Chemistry, Merck Research Laboratories, WP14-2, West Point, PA 19486, USA.
Abstract:
The alpha(v)beta(3) integrin is a non-covalent, heterodimeric, cell-surface protein that is expressed with varying density on numerous cell types, including osteoclasts, vascular smooth muscle cells, endothelial cells and a variety of tumour cells. Functionally, alpha(v)beta(3) mediates a diverse range of biological events including the adhesion of osteoclasts to bone matrix, smooth muscle cell migration and angiogenesis. Specifically, there has been significant attention focused on the preparation of inhibitors of alpha(v)beta(3) for use as inhibitors of bone resorption, in recognition of the medical need for improved prevention and treatment of osteoporosis. Herein, we summarise the pertinent chemistry and biological advances in the medicinal design and biological evaluation of peptide and small molecule alpha(v)beta(3) antagonists as inhibitors of bone resorption.
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