BioCentury
ARTICLE | Distillery Therapeutics

Infectious disease

November 6, 2018 8:44 PM UTC

In vitro and mouse studies identified an inhibitor of C. difficile TcdB that could help treat C. difficile infection (CDI). Chemical synthesis and in vitro testing of hexakisphosphate analogs of inositol yielded a compound that bound TcdB with a Kd of 4 μM and induced TcdB autoproteolysis with an EC50 of 1.1 μM. In a mouse model of CDI, the compound decreased colonic levels of the inflammation marker myeloperoxidase (MPO) compared with inositol. In another mouse model of CDI, an optimized version of the compound increased survival compared with vehicle. Ongoing work by Inositec AG includes structure-activity relationship studies of the compound...