Is experimental data quality the limiting factor in predicting the aqueous solubility of druglike molecules?

David Palmer; John  Mitchell

doi:10.1021/mp500103r

Is experimental data quality the limiting factor in predicting the aqueous solubility of druglike molecules?

David Palmer, John Mitchell

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Abstract

We report the results of testing Quantitative Structure-Property Relationships (QSPR) that were trained upon the same druglike molecules but two different sets of solubility data: (i) data ex- tracted from several different sources from the published literature, for which the experimental uncertainty is estimated to be 0.6-0.7 log S units (referred to mol/l); (ii) data measured by a sin- gle accurate experimental method (CheqSol), for which experimental uncertainty is typically < 0.05 log S units. Contrary to what might be expected, the models derived from the CheqSol experimental data are not more accurate than those derived from the “noisy” literature data. The results suggest that, at the present time, it is the deficiency of QSPR methods (algorithms and/or descriptor sets), and not, as is commonly quoted, the uncertainty in the experimen- tal measurements, which is the limiting factor in accurately predicting aqueous solubility for pharmaceutical molecules.

Original language	English
Pages (from-to)	2962–2972
Number of pages	11
Journal	Molecular Pharmaceutics
Volume	11
Issue number	8
Early online date	11 Jun 2014
DOIs	https://doi.org/10.1021/mp500103r
Publication status	Published - 2014

Fingerprint

Solubility

Uncertainty

Quantitative Structure-Activity Relationship

Pharmaceutical Preparations

Data Accuracy

Datasets

Keywords

pharmaceutical
rule-of-ﬁve
solubility
bioavailability
QSPR
QSAR
druglike
ADME
Random Forest
dissolution
experimental error
CheqSol
Noyes−Whitney
Henderson−Hasselbalch
polymorph
crystal
machine learning
general solubility equation
ADMET

Cite this

Palmer, D., & Mitchell, J. (2014). Is experimental data quality the limiting factor in predicting the aqueous solubility of druglike molecules? Molecular Pharmaceutics, 11(8), 2962–2972. https://doi.org/10.1021/mp500103r

Palmer, David ; Mitchell, John . / Is experimental data quality the limiting factor in predicting the aqueous solubility of druglike molecules?. In: Molecular Pharmaceutics. 2014 ; Vol. 11, No. 8. pp. 2962–2972.

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title = "Is experimental data quality the limiting factor in predicting the aqueous solubility of druglike molecules?",

abstract = "We report the results of testing Quantitative Structure-Property Relationships (QSPR) that were trained upon the same druglike molecules but two different sets of solubility data: (i) data ex- tracted from several different sources from the published literature, for which the experimental uncertainty is estimated to be 0.6-0.7 log S units (referred to mol/l); (ii) data measured by a sin- gle accurate experimental method (CheqSol), for which experimental uncertainty is typically < 0.05 log S units. Contrary to what might be expected, the models derived from the CheqSol experimental data are not more accurate than those derived from the “noisy” literature data. The results suggest that, at the present time, it is the deficiency of QSPR methods (algorithms and/or descriptor sets), and not, as is commonly quoted, the uncertainty in the experimen- tal measurements, which is the limiting factor in accurately predicting aqueous solubility for pharmaceutical molecules.",

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author = "David Palmer and John Mitchell",

year = "2014",

doi = "10.1021/mp500103r",

language = "English",

volume = "11",

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journal = "Molecular Pharmaceutics",

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Palmer, D & Mitchell, J 2014, 'Is experimental data quality the limiting factor in predicting the aqueous solubility of druglike molecules?', Molecular Pharmaceutics, vol. 11, no. 8, pp. 2962–2972. https://doi.org/10.1021/mp500103r