Stacey L. Becker

TL;DR: It appears that most CNS-active agents demonstrate at least some P-gp-mediated transport that can affect brain concentrations, and unbound plasma concentrations may need to be greater than values projected using receptor affinity data to achieve adequate receptor occupancy for effect.

TL;DR: This work presents a compelling case for its broader application as a phenyl group replacement in scenarios where the aromatic ring count impacts physicochemical parameters and overall drug-likeness.

TL;DR: The present study demonstrates that rapid brain equilibration requires a combination of high BBB permeability and low brain tissue binding, and the strategy to select compounds with rapid brain Equilibration in drug discovery should identify compounds with highBBB permeable and low nonspecific binding in brain tissue.

TL;DR: For quick brain penetration with simple diffusion mechanism compounds, CCSF and Cu,plasma represent Cu,brain equally well; for efflux substrates or slow brain penetration compounds,CCSF appears to be equivalent to or more accurate than Cu, Plasma to representCu,brain.

TL;DR: Subsequent evaluation against the rat DAAO enzyme revealed a divergent SAR versus the human enzyme and may explain the high exposures of drug necessary to achieve significant changes in rat or mouse cerebellum D-serine.