cLogP Calculation

The logP value of a compound, which is the logarithm of its partition coefficient between n-octanol and water, is a well established measure of the compound's hydrophilicity. Low hydrophilicities and therefore high logP values may cause poor absorption or permeation.

It has been shown for compounds to have a reasonable propability of being well absorbt their logP value must not be greater than 5.0. The distribution of calculated logP values of more than 3000 drugs on the market underlines this fact (see diagram).

Actelion's in-house logP calculation method is implemented as increment system adding contributions of every atom based on its atom type. Alltogether the cLogP predicting engine distinguishes 368 atom types which are composed of various properties of the atom itself (atomic no and ring membership) as its direct neighbours (bond type, aromaticity state and encoded atomic no). More than 5000 compounds with experimentally determined logP values were used as training set to optimize the 369 contribution values associated with the atom types.

The correlation plot (see diagram) shows calculated versus experimentally determined logP values of an independent test set of more than 5000 compounds being different from the training set.