Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 59, Issue 10, Pages 1681-1689Publisher
BIRKHAUSER VERLAG AG
DOI: 10.1007/PL00012496
Keywords
ionization; lipophilicity; distribution; solubility; permeability; screening; high-throughput method
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This review begins with a general presentation of the new paradigm of drug discovery, with its emphasis on the rapid identification and elimination of compounds with unsuitable physicochemical and pharmacokinetic properties. The focus of the paper is on the various experimental methods used to determine such key physicochemical properties as ionization, lipophilicity and distribution in isotropic and anisotropic systems, solubility, and permeability across artificial membranes. Both traditional and high-throughput methods are presented and their limits highlighted. The text concludes with the trade-off between quantity/speed in high-throughput screening techniques versus greater data quality in the more labor-intensive methods.
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