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Radioprotective Molecules

08.11.2012
Blocking iodide transport by inhibiting the sodium iodide symporter

Iodide entrapment in the thyroid gland is essential, and plays a key role in dysfunctions such as thyroid and breast cancers, thyroiditis, Graves–Basedow disease, and Hashimoto's disease.

The accidents at Chernobyl and Fukushima have revealed growing public concerns, as exposure to radioactive iodine increases the risk of cancer and birth defects. There is an urgent need to find radioprotective molecules to prevent and treat body contamination.

Yves Ambroise and colleagues at the Biology and Technology Institute (IBiTecS, France) identified an important class of compounds that efficiently block iodide transport by inhibiting the sodium iodide symporter, and their results are reported in ChemMedChem.

During a hit optimization program, they synthesized and tested more than 100 molecules for their capacity to block iodide entrapment in rat thyroid cells. They identified a new lead compound with nanomolar activity and low toxicity. This discovery opens new perspectives for the development of novel anti-thyroid drugs and radioprotective molecules, as well as pharmacological tools for further investigation of iodide traffic at the cellular level.

About the Author

Yves Ambroise is a research group leader in the Biology and Technology Institute (IBiTecS) at the French Alternative Energies and Atomic Energy Commission (CEA). His main areas of interest are chemical biology and drug discovery using techniques such as high-throughput screening, chemical optimization, and target identification by chemical proteomic methods. His research focuses on the mechanism of iodide uptake in the thyroid gland. He is a member of the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT).

Author: Yves Ambroise, Alternative Energies and Atomic Energy Commission, CEA, Gif-sur-Yvette (France), http://www-dsv.cea.fr/institutes/institute-of-biology-and-technology-saclay-ibitec-s/units/molecular-labelling-and-bio-organic-chemistry-scbm/bioorganic-chemistry-laboratory-lcb/transport-and-metabolism-of-iodine-y.-ambroise
Title: Synthesis and Evaluation of 3,4-Dihydropyrimidin-2(1H)-ones as Sodium Iodide Symporter Inhibitors

ChemMedChem 2013, 8, No. 1, Permalink to the article: http://dx.doi.org/10.1002/cmdc.201200417

Yves Ambroise | Wiley-VCH
Further information:
http://www.wiley.com

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