October 21, 2004, 1^st Annual PhysChem Symposium: Early ADME and Medicinal Chemistry

Enhancing Knowledge Through a Combination of In-silico and In-vitro ADME Profiling Assays

Bernard Faller (Novartis Institutes for BioMedical Research)

Abstract

A number of ADME related compound properties can be obtained from in-vitro assays of various complexity and throughput. At the same time, a number of molecular properties can be calculated and therefore the question how to combine the two approaches needs to be addressed. We will not discuss the traditional question when to calculate and when to measure but focus and the added value one can get by combining calculations and measurements.

In the first example, we will show calculated pKa values can be used in combination with the Sirius Gradient Analyzer to generate a high-quality pKa MedChem database.
The second example shows how calculated pKa and ClogP values are used to derive experimental logP values from apparent permeability data collected in a PAMPA assay. The third example shows how calculated properties (pKa and molecular volume) can be used to add a Cheminformatics layer to a PAMPA permeability assay, in order to bring it one step closer to true intestinal perfusion.

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