title: Interpreting physicochemical experimental data sets.
abstract: With the wealth of experimental physicochemical data available to chemoinformaticians from the literature, commercial, and company databases an increasing challenge is the interpretation of such datasets. Subtle differences in experimental methodology used to generate these datasets can give rise to variations in physicochemical property values. Such methodology nuances will be apparent to an expert experimentalist but not necessarily to the data analyst and modeller. This paper describes the differences between common methodologies for measuring the four most important physicochemical properties namely aqueous solubility, octan-1-ol/water distribution coefficient, pK(a) and plasma protein binding highlighting key factors that can lead to systematic differences. Insight is given into how to identify datasets suitable for combining.
authors.affiliation: Oncology and Drug Safety and Metabolism, Innovative Medicines, Mereside, AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK. nicola.colclough@astrazeneca.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: Colclough
authors.affiliation: Oncology and Drug Safety and Metabolism, Innovative Medicines, Mereside, AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Wenlock
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000418:Albumins / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002627:Chemistry, Physical / Q000379:methods*; D016208:Databases, Factual; D001330:Electronic Data Processing / Q000379:methods*; D006801:Humans; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D000418:Albumins; D001798:Blood Proteins; D014867:Water; D020003:1-Octanol
keywords: Aqueous solubility; Data curation; Experimental differences; Lipophilicity; Physicochemical properties; Plasma protein binding; QSA(P)R modelling; pK a