ADMET-score - a comprehensive scoring function for evaluation of chemical drug-likeness.
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The results suggested that the ADMET-score would be a comprehensive index to evaluate chemical drug-likeness, and might be helpful for users to select appropriate drug candidates for further development.Abstract:
Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET), play key roles in drug discovery and development. A high-quality drug candidate should not only have sufficient efficacy against the therapeutic target, but also show appropriate ADMET properties at a therapeutic dose. A lot of in silico models are hence developed for prediction of chemical ADMET properties. However, it is still not easy to evaluate the drug-likeness of compounds in terms of so many ADMET properties. In this study, we proposed a scoring function named the ADMET-score to evaluate drug-likeness of a compound. The scoring function was defined on the basis of 18 ADMET properties predicted via our web server admetSAR. The weight of each property in the ADMET-score was determined by three parameters: the accuracy rate of the model, the importance of the endpoint in the process of pharmacokinetics, and the usefulness index. The FDA-approved drugs from DrugBank, the small molecules from ChEMBL and the old drugs withdrawn from the market due to safety concerns were used to evaluate the performance of the ADMET-score. The indices of the arithmetic mean and p-value showed that the ADMET-score among the three data sets differed significantly. Furthermore, we learned that there was no obvious linear correlation between the ADMET-score and QED (quantitative estimate of drug-likeness). These results suggested that the ADMET-score would be a comprehensive index to evaluate chemical drug-likeness, and might be helpful for users to select appropriate drug candidates for further development.read more
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References
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admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties.
TL;DR: An ADMET structure-activity relationship database that collects, curates, and manages available ADMET-associated properties data from the published literature, and provides a user-friendly interface to query a specific chemical profile, using either CAS registry number, common name, or structure similarity.
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