title: Pharmacology and Clinical Drug Candidates in Redox Medicine.
abstract: CONCLUSIONS
  Oxidative stress is suggested to be a disease mechanism common to a wide range of disorders affecting human health. However, so far, the pharmacotherapeutic exploitation of this, for example, based on chemical scavenging of pro-oxidant molecules, has been unsuccessful.
  
  
  BACKGROUND
  An alternative emerging approach is to target the enzymatic sources of disease-relevant oxidative stress. Several such enzymes and isoforms have been identified and linked to different pathologies. For some targets, the respective pharmacology is quite advanced, that is, up to late-stage clinical development or even on the market; for others, drugs are already in clinical use, although not for indications based on oxidative stress, and repurposing seems to be a viable option.
  
  
  RESULTS
  For all other targets, reliable preclinical validation and drug ability are key factors for any translation into the clinic. In this study, specific pharmacological agents with optimal pharmacokinetic profiles are still lacking. Moreover, these enzymes also serve largely unknown physiological functions and their inhibition may lead to unwanted side effects.
  
  
  CONCLUSIONS
  The current promising data based on new targets, drugs, and drug repurposing are mainly a result of academic efforts. With the availability of optimized compounds and coordinated efforts from academia and industry scientists, unambiguous validation and translation into proof-of-principle studies seem achievable in the very near future, possibly leading towards a new era of redox medicine.
authors.affiliation: 1 Cardiovascular Research Institute Maastricht (CARIM), Maastricht University , Maastricht, the Netherlands .
authors.forename: V Thao-Vi
authors.initials: VT
authors.lastname: Dao
authors.affiliation: 1 Cardiovascular Research Institute Maastricht (CARIM), Maastricht University , Maastricht, the Netherlands .
authors.forename: Ana I
authors.initials: AI
authors.lastname: Casas
authors.affiliation: 2 Victor Chang Cardiac Research Institute, and School of Medical Sciences, University of New South Wales , Sydney, Australia .
authors.forename: Ghassan J
authors.initials: GJ
authors.lastname: Maghzal
authors.affiliation: 3 Department of Pathology and Immunology, Medical School, University of Geneva , Geneva, Switzerland .
authors.forename: Tamara
authors.initials: T
authors.lastname: Seredenina
authors.affiliation: 4 Neuroscience Institute , CNR, Padova, Italy .
authors.forename: Nina
authors.initials: N
authors.lastname: Kaludercic
authors.affiliation: 5 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , ISCIII, Madrid, Spain .|6 Instituto de Investigaciones Biomédicas "Alberto Sols" UAM-CSIC , Madrid, Spain .|7 Instituto de Investigación Sanitaria La Paz (IdiPaz) , Madrid, Spain .|8 Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid , Madrid, Spain .
authors.forename: Natalia
authors.initials: N
authors.lastname: Robledinos-Anton
authors.affiliation: 4 Neuroscience Institute , CNR, Padova, Italy .|9 Department of Biomedical Sciences, University of Padova , Padova, Italy .
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
authors.affiliation: 2 Victor Chang Cardiac Research Institute, and School of Medical Sciences, University of New South Wales , Sydney, Australia .
authors.forename: Roland
authors.initials: R
authors.lastname: Stocker
authors.affiliation: 10 Division of Clinical and Laboratory Investigation, Brighton and Sussex Medical School , Brighton, United Kingdom .
authors.forename: Pietro
authors.initials: P
authors.lastname: Ghezzi
authors.affiliation: 3 Department of Pathology and Immunology, Medical School, University of Geneva , Geneva, Switzerland .
authors.forename: Vincent
authors.initials: V
authors.lastname: Jaquet
authors.affiliation: 5 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , ISCIII, Madrid, Spain .|6 Instituto de Investigaciones Biomédicas "Alberto Sols" UAM-CSIC , Madrid, Spain .|7 Instituto de Investigación Sanitaria La Paz (IdiPaz) , Madrid, Spain .|8 Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid , Madrid, Spain .
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuadrado
authors.affiliation: 1 Cardiovascular Research Institute Maastricht (CARIM), Maastricht University , Maastricht, the Netherlands .
authors.forename: Harald H H W
authors.initials: HH
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species