ARTICLE | Distillery Therapeutics

Therapeutics: Clostridium difficile toxin B (TcdB)

October 15, 2015 7:00 AM UTC

In vitro and mouse studies suggest ebselen could be repurposed to treat Clostridium difficile infection (CDI). Screening of a small molecule library in an assay for binding to the cysteine protease domain of TcdB identified ebselen as a TcdB inhibitor (IC50 = 6.9 nM). In a mouse model of TcdB-induced toxicity, ebselen decreased toxicity and increased survival compared with vehicle. In a mouse model of CDI, ebselen decreased inflammatory cell infiltration and pathology in the intestine compared with vehicle. Next steps could include testing ebselen in additional animal models of CDI.

Sound Pharmaceuticals Inc. has ebselen (SPI-3005), a small molecule mimic of glutathione peroxidase (GPX), in Phase II testing for chemotherapy-induced hearing loss...