Database for drug metabolism and comparisons, NICEdrug.ch, aids discovery and design

The discovery of a new drug can take up to 14 years and enormous research efforts and financial investments, with a high risk of failure. To reduce this burden, we developed the NICEdrug.ch database, which incorporates 250,000 bioactive molecules, and studies their metabolic targets, fate, and toxicity. NICEdrug.ch includes a new reactive site centric fingerprint to identify reactive similarity between drug/drug and drug/metabolite pairs. We use NICEdrug.ch to identify all potential inhibited enzymes by the anticancer drug 5fluorouracil, explain new reasons for its toxicity, and suggest avenues to alleviate its side effects. We validate clustering based on reactive site centric fingerprint in statins and identify drugs for repurposing. Last, we propose shikimate 3phosphate to target liver-stage malaria parasites with minimal impact on the human host cell. The NICEdrug.ch database is accessible online for researchers and clinicians to systematically identify reactivity of new small molecules and druggable enzymes with practical applications in lead discovery and drug repurposing.