Results
Title

Computer-Aided Estimation of Biological Activity Profiles of Drug-Like Compounds Taking into Account Their Metabolism in Human Body.

Authors

Filimonov, Dmitry A.; Rudik, Anastassia V.; Dmitriev, Alexander V.; Poroikov, Vladimir V.

Abstract

Most pharmaceutical substances interact with several or even many molecular targets in the organism, determining the complex profiles of their biological activity. Moreover, due to biotransformation in the human body, they form one or several metabolites with different biological activity profiles. Therefore, the development and rational use of novel drugs requires the analysis of their biological activity profiles, taking into account metabolism in the human body. In silico methods are currently widely used for estimating new drug-like compounds' interactions with pharmacological targets and predicting their metabolic transformations. In this study, we consider the estimation of the biological activity profiles of organic compounds, taking into account the action of both the parent molecule and its metabolites in the human body. We used an external dataset that consists of 864 parent compounds with known metabolites. It is shown that the complex assessment of active pharmaceutical ingredients' interactions with the human organism increases the quality of computer-aided estimates. The toxic and adverse effects showed the most significant difference: reaching 0.16 for recall and 0.14 for precision.

Subjects

HUMAN body; DRUG analysis; METABOLISM; BIOTRANSFORMATION (Metabolism); SOCIAL interaction; ORGANIC compounds

Publication

International Journal of Molecular Sciences, 2020, Vol 21, Issue 20, p7492

ISSN

1661-6596

Publication type

Academic Journal

DOI

10.3390/ijms21207492