Virtual Screening for the Discovery of Microbiome Beta-Glucuronidase Inhibitors to Alleviate Cancer Drug Toxicity

The study aimed to address the issue of serious adverse events (SAEs) like hair loss and gastrointestinal problems caused by anti-cancer drugs, which are often reactivated in the gut by β-glucuronidase (βGUS) enzymes from gut bacteria. Researchers used structure-based virtual high-throughput screening (vHTS) to discover novel βGUS inhibitors, screening nearly 400,000 compounds and identifying 69 with positive inhibitory activity. This approach showed a 24% hit rate and suggested potential for developing therapeutic adjuncts to reduce drug-induced gut toxicity, potentially improving adherence to cancer treatment regimens.