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Editorial Board Chairs: Antonello Mai, Rainer Metternich. Assoc. Editors: David Peralta, Scott Williams (Sr)
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ISI Journal Citation Reports © Ranking: 2015: 18/59 (Chemistry Medicinal); 77/255 (Pharmacology & Pharmacy)
Online ISSN: 1860-7187
November 06, 2012
VIP: Synthesis and Evaluation of 3,4-Dihydropyrimidin-2(1H)-ones as Sodium Iodide Symporter Inhibitors
Pierre Lacotte, Celine Puente, Yves Ambroise*
Iodide entrapment in the thyroid gland is essential in vertebrates. It plays a key role in many thyroid and extra-thyroid dysfunctions including thyroid and breast cancers, thyroiditis, Graves–Basedow disease, and Hashimoto's disease. Furthermore, the accidents at Chernobyl and Fukushima have revealed a growing concern among the public, because exposure to radioactive iodine species increases the risk of cancer and birth defects. Today there is an urgent need to find radioprotective molecules to prevent and treat body contamination. Yves Ambroise and Pierre Lacotte at the Biology and Technology Institute (IBiTecS, France) have identified an important class of compounds that efficiently block iodide transport by inhibiting the sodium iodide symporter. 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.
Received September 12, 2012; published online November 6, 2012, DOI: 10.1002/cmdc.201200417.