title: The early research and development of ebselen.
abstract: 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.), 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.
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group for Translational Medicine and Pharmacology TMP, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parnham
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
mesh_terms: D000818:Animals; D001393:Azoles / Q000266:history* / Q000494:pharmacology / Q000627:therapeutic use; D035843:Biomedical Research / Q000266:history*; D002986:Clinical Trials as Topic / Q000266:history; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D054833:Isoindoles; D016566:Organoselenium Compounds / Q000266:history* / Q000494:pharmacology / Q000627:therapeutic use; D018675:Toxicity Tests / Q000266:history
chemical_list: D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen
keywords: Enzyme mimic; Glutathione peroxidase; PZ-51; Selenium; Selenoorganic compounds