A Versatile Method to Determine the Cellular Bioavailability of Small-Molecule Inhibitors.

ABSTRACT: The determination of the cellular bioavailability of small-molecule inhibitors is a critical step for interpreting cell-based data and guiding inhibitor optimization. Herein, a HPLC-MS based protocol was developed to determine inhibitor cellular bioavailability. This generalizable protocol allows determination of the accurate intracellular concentrations and characterization of various properties of inhibitors including the extra- and intracellular stability, the dose- and time-dependence of the intracellular concentrations, the cell permeability, and the nonspecific binding with the cell culture plates, the extracellular matrices, and the cell membrane. The inhibitors of the protein-protein interactions, bromodomains, and the β-catenin/B-cell lymphoma 9 (BCL9) interaction were used to exa

SUBMITTER: Teuscher KB 

PROVIDER: S-EPMC7771553 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature