The Novel DNA Binding Mechanism of Ridinilazole, a Precision Clostridiodes difficile Antibiotic

Abstract

Clostridioides difficile infection (CDI) causes substantial morbidity and mortality worldwide with limited antibiotic treatment options. Ridinilazole is a precision bisbenzimidazole antibiotic being developed to treat CDI and reduce unacceptably high rates of infection recurrence in patients.

A Review of Antibacterial Candidates with New Modes of Action

“…It was also reported in a preprint that 60 bound to and inhibited several essential promoters on the S. aureus chromosome, potentially indicating multiple MoAs . Another minor groove binder is ridinilazole ( 61 ), a symmetrical head-to-head bis-benzimidazole, which was also previously in development for CDI. , Again, multiple MoAs might be in effect, as RNA-seq data indicated that 61 also had broad effects on multiple C. difficile compartments, particularly pathways involved in energy generation . Ridinilazole ( 61 ) completed two phase 3 trials (NCT03595553, NCT03595566) in 2021, but a prespecified superiority threshold was not met, and Summit has halted further development…”