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2015 ; 23
(14
): 1113-29
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Pharmacology and Clinical Drug Candidates in Redox Medicine
#MMPMID26415051
Dao VT
; Casas AI
; Maghzal GJ
; Seredenina T
; Kaludercic N
; Robledinos-Anton N
; Di Lisa F
; Stocker R
; Ghezzi P
; Jaquet V
; Cuadrado A
; Schmidt HH
Antioxid Redox Signal
2015[Nov]; 23
(14
): 1113-29
PMID26415051
show ga
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.
|Animals
[MESH]
|Antioxidants/*pharmacology/therapeutic use
[MESH]
|Drug Design
[MESH]
|Drug Evaluation, Preclinical
[MESH]
|Enzyme Inhibitors/*pharmacology/therapeutic use
[MESH]