The early research and development of ebselen

Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one; PZ-51, DR-3305), is an organoselenium compound with glutathione peroxidase (GPx)-like, thiol-dependent, hydroperoxide reducing activity. As an enzyme mimic for activity of the selenoenzyme GPx, this compound has proved to be highly useful in research...

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Bibliographic Details
Published in:Biochemical pharmacology 2013-11, Vol.86 (9), p.1248-1253
Main Authors: Parnham, Michael J., Sies, Helmut
Format: Article
Language:English
Subjects:
Animals
Azoles - history
Azoles - pharmacology
Azoles - therapeutic use
bile
Biomedical Research - history
brain
Clinical Trials as Topic - history
early development
Enzyme mimic
Glutathione peroxidase
History, 20th Century
History, 21st Century
Humans
industry
ischemia
metabolites
Organoselenium Compounds - history
Organoselenium Compounds - pharmacology
Organoselenium Compounds - therapeutic use
pharmacology
PZ-51
research and development
Selenium
Selenoorganic compounds
stroke
thiols
toxicity
Toxicity Tests - history
toxicology
urine
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Summary:Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one; PZ-51, DR-3305), is an organoselenium compound with glutathione peroxidase (GPx)-like, thiol-dependent, hydroperoxide reducing activity. As an enzyme mimic for activity of the selenoenzyme GPx, this compound has proved to be highly useful in research on mechanisms in redox biology. Furthermore, the reactivity of ebselen with protein thiols has helped to identify novel, selective targets for inhibitory actions on several enzymes of importance in pharmacology and toxicology. Importantly, the selenium in ebselen is not released and thus is not bioavailable, ebselen metabolites being excreted in bile and urine. As a consequence, initial concerns about selenium toxicity, fortunately, were unfounded. Potential applications in medical settings have been explored, notably in brain ischemia and stroke. More recently, there has been a surge in interest as new medical applications have been taken into consideration. The first publication on the biochemical effects of ebselen appeared 30 years ago (Müller et al. [4]), which prompted the authors to retrace the early development from their perspective. It is a fascinating example of fruitful interaction between research-oriented industry and academia
ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2013.08.028