Three-dimensional quantitative structure activity relationship analyses of substrates for CYP2B6. J Pharmacol Exp Ther

To begin to build an understanding of the interactions of CYP2B6 with substrates, two different 3-dimensional quantita-tive structure activity relationship (3D-QSAR) models were con-structed using 16 substrates of B-lymphoblastoid expressed CYP2B6. A pharmacophore model was built using the program Catalyst, which was compared with a partial least-squares (PLS) model using molecular surface-weighted holistic invariant molecular (MS-WHIM) descriptors. The Catalyst model yielded a 3-dimensional model of the common structural features of CYP2B6 substrates, whereas PLS MS-WHIM generated a model based on statistical analyses of molecular descriptors for size and shape of the substrate. The pharmacophore model obtained with Catalyst consisted of three hydrophobes and one hydrogen bond acceptor region. The cross-validated PLS MS