bimosiamose-disodium and Pulmonary-Disease--Chronic-Obstructive

Airway inflammation is a hallmark of respiratory diseases such as asthma and chronic obstructive pulmonary disease. Cell adhesion molecules play critical roles in the recruitment and migration of cells to sites of inflammation. Not surprisingly, these receptors have garnered the attention of the pharmaceutical industry as targets for the development of drugs to treat inflammatory and autoimmune diseases. Although several potential cell adhesion targets exist, development of compounds for pulmonary indications has centered around the selectins and the integrin VLA-4. In vitro and in vivo studies have implicated these receptors in the recruitment of inflammatory cells to the lung as well as to key cellular activation pathways. Several first generation compounds are currently in clinical development for asthma. Positive data from a phase II clinical trial using an inhaled formulation of a selectin antagonist has recently been reported. Initial results from clinical trials using first generation VLA-4 antagonists have been less promising but additional trials with more fully optimized compounds are underway. Results from these trials will provide insight into what the future holds for this exciting new class of drugs to treat pulmonary diseases.

Topics: Animals; Asthma; Biphenyl Compounds; Cell Adhesion Molecules; Chemistry, Pharmaceutical; Clinical Trials as Topic; Humans; Integrin alpha4beta1; Mannose; Mannosides; Phenylalanine; Pulmonary Disease, Chronic Obstructive; Selectins

Inhibition of selectin function is expected to aid in the management of diseases characterized by aberrant or chronic inflammation, as in asthma and chronic obstructive pulmonary disease (COPD). Selectin-mediated adhesion of leukocytes to the vascular endothelium is a critical early event in the initiation of the inflammatory response, making it a good target for therapeutic intervention. Many approaches to modulating selectin function have been explored, including competitive inhibition, altering cell-surface expression and inducing shedding/cleavage from the cell surface; however, clinical success has been elusive.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Biphenyl Compounds; Cell Adhesion; Chemotaxis, Leukocyte; Clinical Trials as Topic; Endothelium, Vascular; Humans; Inflammation; Leukocytes; Ligands; Lung; Mannose; Mannosides; Membrane Glycoproteins; Oligosaccharides; Pulmonary Disease, Chronic Obstructive; Selectins; Sialyl Lewis X Antigen