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Updated: Sep 23, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Yes SIR! On the structure-inactivity relationships in drug discovery
Edgar López-López1, Eli Fernández-de Gortari2, José L Medina-Franco3
1DIFACQUIM Research Group, Department of Pharmacy, School of Chemistry, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; Department of Chemistry and Graduate Program in Pharmacology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07000, Mexico.
Abstract:
In analogy with structure-activity relationships (SARs), which are at the core of medicinal chemistry, studying structure-inactivity relationships (SIRs) is essential to understanding and predicting biological activity. Current computational methods should predict or distinguish 'activity' and 'inactivity' with the same confidence because both concepts are complementary. However, the lack of inactivity data, in particular in the public domain, limits the development of predictive models and its broad application. In this review, we encourage the scientific community to disclose and analyze high-confidence activity data considering both the labeled 'active' and 'inactive' compounds.
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