Pharmacology and Clinical Drug Candidates in Redox Medicine

V. Thao-Vi Dao*, Ana I. Casas, Ghassan J. Maghzal, Tamara Seredenina, Nina Kaludercic, Natalia Robledinos-Anton, Fabio Di Lisa, Roland Stocker, Pietro Ghezzi, Vincent Jaquet, Antonio Cuadrado, Harald H. H. W. Schmidt

*Corresponding author for this work

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Abstract

Significance: 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. Recent Advances: 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. Critical Issues: 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. Future Directions: 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. Antioxid. Redox Signal. 23, 1113-1129.
Original languageEnglish
Pages (from-to)1113-1129
JournalAntioxidants & Redox Signaling
Volume23
Issue number14
DOIs
Publication statusPublished - 10 Nov 2015

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