Computational Model To Predict the Fraction of Unbound Drug in the Brain

Knowing the value of the unbound
drug fraction in the brain (fu,brain)
is essential in estimating its effects
and toxicity on the central nervous system (CNS); however, no model
to predict fu,brain without experimental
procedures is publicly available. In this study, we collected 253
measurements from the literature and an open database and built in
silico models to predict fu,brain using
only freely available software. By selecting appropriate descriptors,
training, and evaluation, our model showed an acceptable performance
on a test data set (R2 = 0.630, percentage
of compounds predicted within a 3-fold error: 69.4%) using chemical
structure alone. Our model is available at https://drumap.nibiohn.go.jp/fubrain/, and all of our data sets can be obtained from the Supporting Information.