Ralph E. Davidson

TL;DR: It is demonstrated that in vitro transporter assays help in understanding the role of P-glycoprotein-mediated efflux activity in determining the disposition of CNS drugs in vivo, and the transwell assay is a valuable in vitro assay to evaluate human P-gp interaction with compounds for assessing brain penetration of new chemical entities to treat CNS disorders.

TL;DR: A new cell line, MDCKII-LE (low efflux), has been developed by selecting a subpopulation of low-efflux cells from MDCkII-WT using an iterative fluorescence-activated cell sorting technique with calcein-AM as a Pgp and efflux substrate.

TL;DR: In vitro ADME screening can generate large quantities of data obtained under identical conditions to allow building of reliable in silico models.

TL;DR: Investigation of likely explanations for clinically observed adverse liver effects of CP-724,714 suggests inhibition of hepatic efflux transporters contributed to hepatic accumulation of drug and bile constituents leading to hepatocellular injury and hepatobiliary cholestasis.

TL;DR: This assay provides an efficient, high throughput means to identifyABCG2 substrates in drug discovery and indicates that a compound tested at 2 microM can be considered a substrate of ABCG2 if its ratio of ratios is > 1.2.