A Bidirectional Permeability Assay for beyond Rule of 5 Compounds.

ABSTRACT: Bidirectional permeability measurement with cellular models grown on Transwell inserts is widely used in pharmaceutical research since it not only provides information about the passive permeability of a drug, but also about transport proteins involved in the active transport of drug substances across physiological barriers. With the increasing number of investigative drugs coming from chemical space beyond Lipinski's Rule of 5, it becomes more and more challenging to provide meaningful data with the standard permeability assay. This is exemplified here by the difficulties we encountered with the cyclic depsipeptides emodepside and its close analogs with molecular weight beyond 1000 daltons and cLogP beyond 5. The aim of this study is to identify potential reasons for these challenges and

SUBMITTER: Cui Y 

PROVIDER: S-EPMC8400635 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature