SuperCYPsPred—a web server for the prediction of cytochrome activity

Abstract

Abstract Cytochrome P450 enzymes (CYPs)-mediated drug metabolism influences drug pharmacokinetics and results in adverse outcomes in patients through drug–drug interactions (DDIs). Absorption, distribution, metabolism, excretion and toxicity (ADMET) issues are the leading causes for the failure of a drug in the clinical trials. As details on their metabolism are known for just half of the approved drugs, a tool for reliable prediction of CYPs specificity is needed. The SuperCYPsPred web server is currently focused on five major CYPs isoenzymes, which includes CYP1A2, CYP2C19, CYP2D6, CYP2C9 and CYP3A4 that are responsible for more than 80% of the metabolism of clinical drugs. The prediction models for classification of the CYPs inhibition are based on well-established machine learning methods. The models were validated both on cross-validation and external validation sets and achieved good performance. The web server takes a 2D chemical structure as input and reports the CYP inhibition profile of the chemical for 10 models using different molecular fingerprints, along with confidence scores, similar compounds, known CYPs information of drugs—published in literature, detailed interaction profile of individual cytochromes including a DDIs table and an overall CYPs prediction radar chart (http://insilico-cyp.charite.de/SuperCYPsPred/). The web server does not require log in or registration and is free to use.