Optibrium, a prominent developer of software and AI solutions for drug discovery, has unveiled a groundbreaking study published in the journal Xenobiotica, presenting a novel method that significantly enhances the prediction of routes of metabolism and metabolites in early drug discovery stages. The accurate prediction of drug metabolism is crucial in preventing late-stage failures and drug withdrawals. Early identification of dominant metabolism pathways greatly enhances the chances of drug success.
The study introduces Optibrium’s innovative WhichEnzyme™ model, which successfully predicts the enzyme families most likely to metabolize a drug candidate. This model is combined with previously published models, including regioselectivity models for key Phase I and Phase II drug-metabolizing enzymes, utilizing quantum mechanical simulations and machine learning. The WhichP450 model predicts specific Cytochrome P450 isoforms responsible for a compound’s metabolism.
By integrating these model outputs, Optibrium presents a new method for determining the most likely routes of metabolism and corresponding metabolites that can be experimentally observed. The study demonstrates that this method excels in identifying reported metabolites with high sensitivity and precision compared to alternative methods for predicting in vivo metabolite profiles. This advancement allows researchers to identify compounds with improved metabolic stability and enhanced safety profiles, aligning with Optibrium’s recently launched StarDrop Metabolism module. Dr. Mario Öeren, Principal Scientist at Optibrium, expresses enthusiasm for the study’s findings, highlighting its six years of focused research resulting in a practical model for predicting metabolic pathways.
“Through carefully curated datasets and our signature reactivity-accessibility approach, we have developed accurate isoform-specific regioselectivity models for the vital Phase I and Phase II enzyme families.”
Dr. Mario Öeren, Principal Scientist, Optibrium
The publication of this study marks a significant milestone in drug discovery, providing researchers with a powerful tool for predicting drug metabolism. Optibrium’s breakthrough method offers new insights and innovative solutions that could revolutionize the efficiency and success rates of pharmaceutical development. The models included in the module have greater accuracy and transferability than conventional QSAR methods, allowing the identification of sites of metabolism for key enzymes across human Phase I and II metabolism and common preclinical species.
