Physicochemical Properties in Drug Profiling

Caco-2 adenocarcinoma cell line derived from human colon 

FaSSIF fasted-state simulated artificial intestinal fluid 

Molecular Drug Properties. Measurement and Prediction. R. Mannhold (Ed.) Copyright 2008 Wiley-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-31755-4 

Alog P difference between log P in octanol-water and alkane-water 

Elog D experimental log D based on a high-performance liquid 

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Kerns EH (2001) High Throughput Physicochemical Profiling for Drug Discovery. J Pharm Sci 90(11) 1838-1858 Kibbey CE, Poole SK, Robinson B et al. (2001) An Integrated Process for Measuring The Physicochemical Properties of Drug Candidates in a Preclinical Discovery Environment. J Pharm Sci 90(8) 1164-1175... 

Prediction of various physicochemical properties such as solubihty, lipophhicity log P, pfQ, number of H-donor and acceptor atoms, number of rotatable bonds, polar surface area), drug-likeness, lead-likeness, and pharmacokinetic properties (ADMET profile). These properties can be applied as a filter in the prescreening step in virtual screening. 

Van de Waterbeemd, H. Property-based lead optimization. In Biological and Physicochemical Profiling in Drug Research, Testa, B., Kramer, S. D., Wunderli-Allenspach, H., Folkers, G. (eds.), VHCA, Zurich and Wiley-VCH, Weinheim, 2006, pp. 25-45. 

This chapter considered ionizable drug-like molecules. Absorption properties that are influenced by the pKj were explored. The impact of the pKj-absorption relationship on key physicochemical profiling underlying absorption (solubihty, per-meabihty and ionization) was examined in detail and several simpUfying equations were discussed. The various diff relationships considered in the chapter are systematized in Table 3.2. Table 3.3 summarizes the apparent pfQ shift method for detecting aggregates in solubility profiles, when the apparent pff value derived from Henderson-Hasselbalch analysis of log S pH profile does not agree with the... 

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