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.
Biochem Pharmacol. 2013 Nov 1;86(9):1248-53. doi: 10.1016/j.bcp.2013.08.028. Epub 2013 Sep 5.
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.
依布硒啉(2-苯基-1,2-苯并异硒唑-3(2H)-酮;PZ-51,DR-3305)是一种有机硒化合物,具有谷胱甘肽过氧化物酶(GPx)样、依赖巯基、过氧化物还原活性。作为硒酶 GPx 活性的酶模拟物,该化合物已被证明在氧化还原生物学机制的研究中非常有用。此外,依布硒啉与蛋白质巯基的反应性有助于确定对药理学和毒理学中几种重要酶的抑制作用的新的、选择性靶标。重要的是,依布硒啉中的硒不会释放,因此不可生物利用,依布硒啉代谢物在胆汁和尿液中排泄。因此,最初对硒毒性的担忧是没有根据的。已经探索了在医疗环境中的潜在应用,特别是在脑缺血和中风方面。最近,由于考虑了新的医学应用,人们的兴趣大增。30 年前(Müller 等人)发表了关于依布硒啉生化作用的第一篇出版物,这促使作者从他们的角度追溯早期的发展。这是一个令人着迷的例子,说明了面向研究的行业和学术界之间富有成效的互动。