Angela C. Doran

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: 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: characterized 3-(3-chloro-phenoxymethyl)-1-(tetrahydro-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin- 4-ylamine (PF-4800567), a novel and potent inhibitor of CK1ϵ with greater than 20-fold selectivity over CK1δ that should prove useful in probing unique roles between these two kinases in multiple signaling pathways

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: Human microsomal clearance and suboptimal physicochemical properties of the initial lead were improved to give potent, metabolically stable and orally available mGluR2 PAMs.