Targeting selectins for the treatment of respiratory diseases.
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.
Romano
S J
SJ
Departments of Biology, Ontogen Corporation, Carlsbad, CA 92009, USA. sue.romano@ontogen.com
Slee
D H
DH
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001713:Biphenyl Compounds / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002986:Clinical Trials as Topic; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology; D008024:Ligands; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008358:Mannose / Q000031:analogs & derivatives; D008362:Mannosides / Q000627:therapeutic use; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D019087:Selectins / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen
D018927:Anti-Asthmatic Agents; D001713:Biphenyl Compounds; D008024:Ligands; D008362:Mannosides; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; C108700:bimosiamose disodium; D008358:Mannose