title: Neutrophil elastase inhibitors.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) constitutes a worldwide health problem. There is currently an urgent and unmet need for the development of small molecule therapeutics capable of blocking and/or reversing the progression of the disorder. Recent studies have greatly illuminated our understanding of the multiple pathogenic processes associated with COPD. Of paramount importance is the key role played by proteases, oxidative stress, apoptosis and inflammation. Insights gained from these studies have made possible the exploration of new therapeutic approaches.
  
  
  METHODS
  An overview of major developments in COPD research with emphasis on low-molecular mass neutrophil elastase inhibitors is described in this review.
  
  
  CONCLUSIONS
  Great strides have been made toward our understanding of the biochemical and cellular events associated with COPD. However, our knowledge regarding the inter-relationships among the multiple pathogenic mechanisms and their mediators involved is still limited. The problem is further compounded by the unavailability of suitable validated biomarkers for assessing the efficacy of potential therapeutic interventions. The complexity of COPD suggests that effective therapeutic interventions may require the administration of more than one agent such as a human neutrophil elastase or MMP-12 inhibitor with an anti-inflammatory agent such as a PDE4 inhibitor or a dual function agent capable of disrupting the cycle of proteolysis, apoptosis, inflammation and oxidative stress.
authors.affiliation: Wichita State University, Department of Chemistry, Wichita, KS 67260, USA. bill.groutas@wichita.edu
authors.forename: William C
authors.initials: WC
authors.lastname: Groutas
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Dou
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Alliston
mesh_terms: D000818:Animals; D006801:Humans; D019272:Leukocyte Elastase / Q000502:physiology; D053491:Proteinase Inhibitory Proteins, Secretory / Q000494:pharmacology / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; D019272:Leukocyte Elastase