title: FG-4497: a new target for acute respiratory distress syndrome?
abstract: The morbidity and mortality rates associated with acute respiratory distress syndrome (ARDS) remain high and the development of new therapeutic strategies is urgently required. Some pharmacological treatments, proposed or under evaluation for ARDS, seek to protect the endothelium and consequently mitigate fluid extravasation into the alveolar space. FG-4497 is a new compound which acts as a prolyl hydroxylase domain 2 inhibitor and mimics hypoxia in the activation of hypoxia-inducible factor-2α signaling, decreasing VE-cadherin phosphorylation and thus promoting integrity of adherens junctions. In this special report, we discuss the pharmacological characteristics of FG-4497, its effect on lung parenchyma and other organs and future perspectives in ARDS. In short, FG-4497 may be considered a novel pharmacological option targeting endothelial cell repair in lung diseases such as ARDS. Further experimental and clinical studies are warranted to better understand the mechanisms of action of FG-4497 in different types of lung injury.
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, Brazil.
authors.forename: Pedro Leme
authors.initials: PL
authors.lastname: Silva
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000037:antagonists & inhibitors*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004791:Enzyme Inhibitors; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D000099162:Endothelial PAS Domain-Containing Protein 1; C490190:EGLN1 protein, human
keywords: VE-cadherin; acute respiratory distress syndrome; adherens junctions; endothelium; hypoxia