title: Molecular determinants of blood-brain barrier permeation.
abstract: The blood-brain barrier (BBB) is a microvascular unit which selectively regulates the permeability of drugs to the brain. With the rise in CNS drug targets and diseases, there is a need to be able to accurately predict a priori which compounds in a company database should be pursued for favorable properties. In this review, we will explore the different computational tools available today, as well as underpin these to the experimental methods used to determine BBB permeability. These include in vitro models and the in vivo models that yield the dataset we use to generate predictive models. Understanding of how these models were experimentally derived determines our accurate and predicted use for determining a balance between activity and BBB distribution.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University (NEOMED), Rootstown, OH 44272, USA.
authors: Werner J
authors: WJ
authors: Geldenhuys
authors: Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26505, USA.
authors: Afroz S
authors: AS
authors: Mohammad
authors: Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26505, USA.
authors: Chris E
authors: CE
authors: Adkins
authors: Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26505, USA.
authors: Paul R
authors: PR
authors: Lockman
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000187:drug effects; D003198:Computer Simulation; D016503:Drug Delivery Systems; D006801:Humans; D010539:Permeability
keywords: high-throughput; in silico; logPS; nutrient transporters; virtual screening