Quantifying the chemical beauty of drugs

G. Richard Bickerton, Gaia V. Paolini, Jeremy Besnard, Sorel Muresan, Andrew L. Hopkins (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    398 Citations (Scopus)

    Abstract

    Drug-likeness is a key consideration when selecting compounds during the early stages of drug discovery. However, evaluation of drug-likeness in absolute terms does not reflect adequately the whole spectrum of compound quality. More worryingly, widely used rules may inadvertently foster undesirable molecular property inflation as they permit the encroachment of rule-compliant compounds towards their boundaries. We propose a measure of drug-likeness based on the concept of desirability called the quantitative estimate of drug-likeness (QED). The empirical rationale of QED reflects the underlying distribution of molecular properties. QED is intuitive, transparent, straightforward to implement in many practical settings and allows compounds to be ranked by their relative merit. We extended the utility of QED by applying it to the problem of molecular target druggability assessment by prioritizing a large set of published bioactive compounds. The measure may also capture the abstract notion of aesthetics in medicinal chemistry.

    Original languageEnglish
    Pages (from-to)90-98
    Number of pages9
    JournalNature Chemistry
    Volume4
    Issue number2
    DOIs
    Publication statusPublished - Feb 2012

    Keywords

    • DECISION-MAKING
    • PHYSICOCHEMICAL PARAMETERS
    • MOLECULAR-PROPERTIES
    • MEDICINAL CHEMISTRY
    • MATHEMATICAL-THEORY
    • BINDING-SITES
    • DISCOVERY
    • OPTIMIZATION
    • LIBRARIES
    • DRUGGABILITY

    Cite this

    Bickerton, G. R., Paolini, G. V., Besnard, J., Muresan, S., & Hopkins, A. L. (2012). Quantifying the chemical beauty of drugs. Nature Chemistry, 4(2), 90-98. https://doi.org/10.1038/NCHEM.1243