Current state and future perspectives in QSAR models to predict blood-brain barrier penetration in central nervous system drug R&D

Authors
Morales, Juan Francisco; Scioli Montoto, Sebastián; Fagiolino, Pietro; Ruiz, María Esperanza
Publication Year
2017
Language
English
Format
article
Status
Published version
Description
The Blood-Brain Barrier (BBB) is a physical and biochemical barrier that restricts the entry of certain drugs to the Central Nervous System (CNS), while allowing the passage of others. The ability to predict the permeability of a given molecule through the BBB is a key aspect in CNS drug discovery and development, since neurotherapeutic agents with molecular targets in the CNS should be able to cross the BBB, whereas peripherally acting agents should not, to minimize the risk of CNS adverse effects. In this review we examine and discuss QSAR approaches and current availability of experimental data for the construction of BBB permeability predictive models, focusing on the modeling of the biorelevant parameter unbound partitioning coefficient (Kp,uu). Emphasis is made on two possible strategies to overcome the current limitations of in silico models: considering the prediction of brain penetration as a multifactorial problem, and increasing experimental datasets through accurate and standardized experimental techniques.
Fil: Morales, Juan Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina
Fil: Scioli Montoto, Sebastián. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina
Fil: Fagiolino, Pietro. Universidad de la República; Uruguay
Fil: Ruiz, María Esperanza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina
Subject
BLOOD-BRAIN BARRIER
BRAIN PENETRATION
CENTRAL NERVOUS SYSTEM
IN SILICO MODELS
MICRODIALYSIS
PASSIVE DIFUSSION
PHARMACOKINETIC
PROTEIN BINDING
QSAR MODELS
UNBOUND DRUG FRACTION
Medicina Química
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/72761