Development of synthetic pan-selectin antagonists: a new treatment strategy for chronic inflammation in asthma

Asthma is characterized by chronic inflammation of large and small airways maintained by extravasation of leukocytes from the bloodstream into the surrounding peribronchial tissue. The process of extravasation is of crucial importance in inflammation and is mediated by a sequenced and concerted action between different adhesion molecules on endothelial cells and ligands on leukocytes. In this context, initial rolling and tethering is generally considered to be the primary event which is mediated by selectins, a family of glycoproteins comprised of E-, P- and L-selectin. Their role in asthma has been demonstrated in a variety of animal models, showing that all three selectins are involved in the chronic inflammation in asthma. Therefore, selectins are an attractive target where pan-selectin antagonism is the desired treatment strategy. Here, we give an overview of the status of the preclinical and clinical development of bimosiamose, the most advanced synthetic pan-selectin antagonist as a treatment for asthma.