A simple model to predict blood-brain barrier permeation from 3D molecular fields.
We report a four-component partial least squares discriminant analysis (PLS) model for the prediction of blood-brain barrier (BBB) permeation using descriptors derived from 3D molecular fields. The 3D fields were transformed by VolSurf into suitable 1D descriptors, which were correlated to the ratio of blood-brain partitioning measured at steady state in rats (log C(brain)/C(blood)). The model so obtained sheds light on molecular properties influencing BBB permeation. It can also be used in the virtual screening of new chemicals.
Ooms
Frédéric
F
Institut de Chimie Thérapeutique, Section de Pharmacie, BEP, Université de Lausanne, CH-1015, Lausanne, Switzerland.
Weber
Peter
P
Carrupt
Pierre Alain
PA
Testa
Bernard
B
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D016018:Least-Squares Analysis; D008954:Models, Biological; D010539:Permeability; D010599:Pharmacokinetics; D051381:Rats