title: Novel approaches to pulmonary arterial hypertension drug discovery.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. The goal of drug development for PAH is to develop effective therapies that halt, or ideally, reverse the obliterative vasculopathy that results in vessel loss and obstruction of blood flow to the lungs.
  
  
  METHODS
  This review summarizes the current approach to candidate discovery in PAH and discusses the currently available drug discovery methods that should be implemented to prioritize targets and obtain a comprehensive pharmacological profile of promising compounds with well-defined mechanisms.
  
  
  CONCLUSIONS
  To improve the successful identification of leading drug candidates, it is necessary that traditional pre-clinical studies are combined with drug screening strategies that maximize the characterization of biological activity and identify relevant off-target effects that could hinder the clinical efficacy of the compound when tested in human subjects. A successful drug discovery strategy in PAH will require collaboration of clinician scientists with medicinal chemists and pharmacologists who can identify compounds with an adequate safety profile and biological activity against relevant disease mechanisms.
authors.affiliation: a Division of Pulmonary and Critical Care Medicine, The Vera Moulton Wall Center for Pulmonary Vascular Medicine , Stanford Cardiovascular Institute , Stanford , CA , USA.
authors.forename: Yon K
authors.initials: YK
authors.lastname: Sung
authors.affiliation: a Division of Pulmonary and Critical Care Medicine, The Vera Moulton Wall Center for Pulmonary Vascular Medicine , Stanford Cardiovascular Institute , Stanford , CA , USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Yuan
authors.affiliation: a Division of Pulmonary and Critical Care Medicine, The Vera Moulton Wall Center for Pulmonary Vascular Medicine , Stanford Cardiovascular Institute , Stanford , CA , USA.
authors.forename: Vinicio A
authors.initials: VA
authors.lastname: de Jesus Perez
mesh_terms: D000818:Animals; D003299:Cooperative Behavior; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology
keywords: Pulmonary arterial hypertension; animal models; drug discovery; high content imaging; high throughput screening; pathology; toxicity