The Brain Exposure Efficiency (BEE) Score

The blood-brain barrier (BBB), composed of microvascular
tight
junctions and glial cell sheathing, selectively controls drug permeation
into the central nervous system (CNS) by either passive diffusion
or active transport. Computational techniques capable of predicting
molecular brain penetration are important to neurological drug design.
A novel prediction algorithm, termed the Brain Exposure Efficiency
Score (BEE), is presented. BEE addresses the need to incorporate the
role of trans-BBB influx and efflux active transporters by considering
key brain penetrance parameters, namely, steady state unbound brain
to plasma ratio of drug (Kp,uu) and dose
normalized unbound concentration of drug in brain (Cu,b). BEE was devised using quantitative structure–activity
relationships (QSARs) and molecular modeling studies on known transporter
proteins and their ligands. The developed algorithms are provided
as a user-friendly open source calculator to assist in optimizing
a brain penetrance strategy during the early phases of small molecule
molecular therapeutic design.