Similarity based SAR (SIBAR) as tool for early ADME profiling.

摘要: Estimation of bioavailability and toxicity at the very beginning drug development process is one big challenges in discovery. Most processes involved ADME are driven by rather unspecific interactions between drugs biological macromolecules. Within past decade, transport pumps such as P-glycoprotein (Pgp) have gained increasing interest early profiling process. Due to high structural diversity ligands Pgp, traditional QSAR methods were only successful within analogous series compounds. We used an approach based on similarity calculations predict Pgp-inhibitory activity a propafenone analogues. This SIBAR selection highly diverse reference compound set calculation values these The (denoted descriptors) then for PLS analysis. Our results show, that 131 type compounds, models with good predictivity obtained both cross validation procedures 31-compound external test set. Thus, new descriptors might be versatile tool generation predictive models.