Small-molecule inhibitors of sodium iodide symporter function.
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 nM. 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.
Lecat-Guillet
Nathalie
N
Department of Bioorganic Chemistry and Isotopic Labelling, CEA, Institute of Biology and Technology (iBiTecS), Gif-sur-Yvette 91191, France.
Merer
Goulven
G
Lopez
Roman
R
Pourcher
Thierry
T
Rousseau
Bernard
B
Ambroise
Yves
Y
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005453:Fluorescence; D006801:Humans; D020128:Inhibitory Concentration 50; D007454:Iodides / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D015203:Reproducibility of Results; D054852:Small Molecule Libraries / Q000494:pharmacology*; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013997:Time Factors; D000099209:Sodium-Iodide Symporters
D007454:Iodides; D054852:Small Molecule Libraries; D027981:Symporters; D000099209:Sodium-Iodide Symporters