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Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one, also called PZ-51) is by far the most popular organoselenium compound and since the 1990s it has entered into several clinical trials.1–9  Of particular therapeutic significance, Ebselen has been associated with some borderline beneficial effects in studies related to brain ischemia, stroke, and noise-induced deafness,1,3,5  but so far it has not been approved to be used as a pharmaceutical agent to treat a specific disease or pathology. Despite this, the low toxicity of Ebselen to humans and its marginal beneficial effects in some clinical trials has given new momentum to the synthesis of organoselenium compounds. Here, we will present and discuss the published clinical trials and we will also illustrate the approved or ongoing clinical trials with Ebselen. In each case, we will briefly discuss the chemistry and biochemistry supporting the “authors’ rationale” to test Ebselen in different pathologies. The authors considered the weak glutathione peroxidase-like properties of Ebselen to be the main molecular mechanism mediating Ebselen pharmacology. However, as will become evident, the biochemical behavior of Ebselen is much more complex than a simple low-molecular-mass compound capable of decomposing peroxides after interacting with endogenous thiol-groups in the body.

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