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Small‐Molecule Inhibitors of Sodium Iodide Symporter Function
Author(s) -
LecatGuillet Nathalie,
Merer Goulven,
Lopez Roman,
Pourcher Thierry,
Rousseau Bernard,
Ambroise Yves
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200700682
Subject(s) - sodium iodide symporter , symporter , small molecule , chemistry , iodide , function (biology) , biochemistry , sodium iodide , microbiology and biotechnology , transporter , biology , gene , organic chemistry
The Na + /I − symporter (NIS) mediates iodide uptake into thyroid follicular cells. Although NIS has been cloned and thoroughly studied at the molecular level, the biochemical processes involved in post‐translational regulation of NIS are still unknown. The purpose of this study was to identify and characterize inhibitors of NIS function. These small organic molecules represent a starting point in the identification of pharmacological tools for the characterization of NIS trafficking and activation mechanisms. The screening of a collection of 17 020 druglike compounds revealed new chemical inhibitors with potencies down to 40 n M . Fluorescence measurement of membrane potential indicates that these inhibitors do not act by disrupting the sodium gradient. They allow immediate and total iodide discharge from preloaded cells in accord with a specific modification of NIS activity, probably through distinct mechanisms.