The discovery of a drug requires over a decade of intensive research and financial investments - and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied their enzymatic metabolic targets, fate, and toxicity. NICEdrug.ch includes a unique fingerprint that identifies reactive similarities between drug-drug and drug-metabolite pairs. We validated the application, scope, and performance of NICEdrug.ch over similar methods in the field on golden standard datasets describing drugs and metabolites sharing reactivity, drug toxicities, and drug targets. We use NICEdrug.ch to evaluate inhibition and toxicity by the anticancer drug 5-fluorouracil, and suggest avenues to alleviate its side effects. We propose shikimate 3-phosphate for targeting liver-stage malaria with minimal impact on the human host cell. Finally, NICEdrug.ch suggests over 1300 candidate drugs and food molecules to target COVID-19 and explains their inhibitory mechanism for further experimental screening. The NICEdrug.ch database is accessible online to systematically identify the reactivity of small molecules and druggable enzymes with practical applications in lead discovery and drug repurposing.
The discovery of a drug requires over a decade of intenpan>sive research anpan>d finanpan>cial investmenpan>ts - anpan>d still has a high risk of failure. To reduce this burdenpan>, we developed the NICEdrug.ch resource, which incorporates 250,000 biopan> class="Chemical">active molecules, and studied their enzymatic metabolic targets, fate, and toxicity. NICEdrug.ch includes a unique fingerprint that identifies reactive similarities between drug-drug and drug-metabolite pairs. We validated the application, scope, and performance of NICEdrug.ch over similar methods in the field on golden standard datasets describing drugs and metabolites sharing reactivity, drug toxicities, and drug targets. We use NICEdrug.ch to evaluate inhibition and toxicity by the anticancer drug 5-fluorouracil, and suggest avenues to alleviate its side effects. We propose shikimate 3-phosphate for targeting liver-stage malaria with minimal impact on the human host cell. Finally, NICEdrug.ch suggests over 1300 candidate drugs and food molecules to target COVID-19 and explains their inhibitory mechanism for further experimental screening. The NICEdrug.ch database is accessible online to systematically identify the reactivity of small molecules and druggable enzymes with practical applications in lead discovery and drug repurposing.
Keywords:
E. coli; P. falciparum; computational biology; drug clustering; drug metabolic fate; drug similarity; enzyme inhibition; human; ligand-based drug discovery; medicine; nutraceuticals; systems biology
Authors: Rebecca R Stanway; Ellen Bushell; Anush Chiappino-Pepe; Magali Roques; Theo Sanderson; Blandine Franke-Fayard; Reto Caldelari; Murielle Golomingi; Mary Nyonda; Vikash Pandey; Frank Schwach; Séverine Chevalley; Jai Ramesar; Tom Metcalf; Colin Herd; Paul-Christian Burda; Julian C Rayner; Dominique Soldati-Favre; Chris J Janse; Vassily Hatzimanikatis; Oliver Billker; Volker T Heussler Journal: Cell Date: 2019-11-14 Impact factor: 41.582
Authors: Dulce Catalina Díaz-Quiroz; César Salvador Cardona-Félix; José Luis Viveros-Ceballos; Miguel Angel Reyes-González; Franciso Bolívar; Mario Ordoñez; Adelfo Escalante Journal: J Enzyme Inhib Med Chem Date: 2018-12 Impact factor: 5.051