A Computational Physics-based Approach to Predict Unbound Brain-to-Plasma Partition Coefficient, Kp,uu.
J Chem Inf Model
; 63(12): 3786-3798, 2023 06 26.
Article
en En
| MEDLINE
| ID: mdl-37267072
The blood-brain barrier (BBB) plays a critical role in preventing harmful endogenous and exogenous substances from penetrating the brain. Optimal brain penetration of small-molecule central nervous system (CNS) drugs is characterized by a high unbound brain/plasma ratio (Kp,uu). While various medicinal chemistry strategies and in silico models have been reported to improve BBB penetration, they have limited application in predicting Kp,uu directly. We describe a physics-based computational approach, a quantum mechanics (QM)-based energy of solvation (E-sol), to predict Kp,uu. Prospective application of this method in internal CNS drug discovery programs highlights the utility and accuracy of this new method, which showed a categorical accuracy of 79% and an R2 of 0.61 from a linear regression model.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Barrera Hematoencefálica
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
J Chem Inf Model
Asunto de la revista:
INFORMATICA MEDICA
/
QUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos