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Quantifying the chemical beauty of drugs

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Bickerton, G. Richard, Paolini, Gaia V., Besnard, Jérémy, Muresan, Sorel, Hopkins, Andrew L.·2012·Nature Chemistry

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Abstract

Druglikeness is a key consideration when selecting compounds during the early stages of drug discovery. However, evaluation of druglikeness in absolute terms does not adequately reflect 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 toward their boundaries. We propose a measure of druglikeness based on the concept of desirability called Quantitative Estimate of Druglikeness (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 extend 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.

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“Abbreviations ADAM: Adaptative moment estimation; DRD2: Dopamine receptor D2; FEP: Free energy perturbation; FCD: Fréchet chemnet distance; GPCR: G protein-coupled receptor; QED: Quantitative estimate of drug-likeness; QSAR: Quantitative structure–activity relationship; SAscore: Synthetic accessibility score; SELFIES:…”
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Authors: Bickerton, G. R., Paolini, G. V., Besnard, J., Muresan, S., & Hopkins, A. L.
Venue: Nature Chemistry
Publisher: Springer Science and Business Media LLC
Published: 2012-01-24
Volume: 4
Issue: 2
Pages: 90-98
ISSN: 1755-4330 (ISSN-L)
1755-4349
DOI: 10.1038/nchem.1243
OpenAlex: W2034549041
Cited by: 2,242
References: 7
FWCI: 51.25
Type: journal article
Language: en
Open access: green

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Quantifying the chemical beauty of drugs

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