Selectin antagonists and their potential impact for the treatment of inflammatory lung diseases

Selectin antagonists comprise a heterogeneous group of synthetic molecules, natural product compounds and biologics. They are targeted against the selectin family of cell adhesion molecules (selectins), which are located on the surface of endothelial cells (E- and P-selectin), platelets (P-selectin) and of leukocytes (L-selectin). Selectins play a crucial role in the adhesion and activation of leukocytes and platelets in inflammation. They are supposed to be involved in the pathogenesis of several respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Selectin antagonists targeting one, two or all three selectins (panselectin antagonists) were developed. Depending on the target binding site, sialyl Lewis X (sLex)-mimicking antagonists can be distinguished from antagonists mimicking more complex natural ligand structures like, for example, P-selectin glycoprotein ligand-1 (PSGL-1). To date, the most advanced pan-selectin antagonist in development is Bimosiamose mimicking both sLex and PSGL-1. It has been demonstrated to be effective in animal models of inflammatory lung diseases and human clinical trials for asthma and COPD. Based on the preclinical and clinical experiences with Bimosiamose, this chapter summarizes the potential impact of selectin antagonists for the treatment of inflammatory lung diseases.