Thirty-two structurally diverse drugs used for the treatment of various conditions of the central
nervous system (CNS), along with two active metabolites, and eight non-CNS drugs were …

Quantitative prediction of human pharmacokinetics is critical in assessing the viability of drug
candidates and in determining first‐in‐human dosing. Numerous prediction methodologies…

Cytochrome P450 (P450) 3A4 is the most abundant human P450 enzyme and has broad
selectivity for substrates. The enzyme can show marked catalytic regioselectivity and unusual …

Aberrant regulation of Notch signaling has been implicated in tumorigenesis. Proteolytic
release of the Notch intracellular domain (NICD) by γ-secretase plays a key role in Notch-…

This study was designed 1) to examine the effects of blood-brain barrier (BBB) permeability [quantified
as permeability-surface area product (PS)], unbound fraction in plasma (f u,…

This study was designed to evaluate the use of cerebrospinal fluid (CSF) drug concentration
and plasma unbound concentration (C u,plasma ) to predict brain unbound concentration (…

Organophosphates inactivate acetylcholinesterase by reacting covalently with the active
center serine. We have examined the reactivation of a series of resolved enantiomeric …

Background: The importance of predicting human pharmacokinetics during compound
selection has been recognized in the pharmaceutical industry. To this end there are many …

The availability of a crystal structure and comparative sequences of the cholinesterases has
provided templates suitable for analyzing the molecular bases of specificity of reversible …

Revised Manuscript Received June 19, 1995® abstract: We have examined the specificity
of planar carboxyl and tetrahedral phosphonyl esters for mouse cholinesterases and have …