Is experimental data quality the limiting factor in predicting the aqueous solubility of druglike molecules?
Palmer, David S. and Mitchell, John B. O. (2014) Is experimental data quality the limiting factor in predicting the aqueous solubility of druglike molecules? Molecular Pharmaceutics, 11 (8). 2962–2972. ISSN 1543-8384 (https://doi.org/10.1021/mp500103r)
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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.
ORCID iDs
Palmer, David S. ORCID: https://orcid.org/0000-0003-4356-9144 and Mitchell, John B. O.;-
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Item type: Article ID code: 48972 Dates: DateEvent4 August 2014Published9 July 2014Published Online11 June 2014AcceptedSubjects: Medicine > Pharmacy and materia medica
Medicine > Therapeutics. PharmacologyDepartment: Faculty of Science > Pure and Applied Chemistry Depositing user: Pure Administrator Date deposited: 23 Jul 2014 13:09 Last modified: 11 Oct 2024 00:22 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/48972