Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies

Expert Opinion on Therapeutic Targets
Terry F Davies, Rauf Latif

Abstract

The thyroid-stimulating hormone receptor (TSHR) is the essential molecule for thyroid growth and thyroid hormone production. Since it is also a key autoantigen in Graves' disease and is involved in thyroid cancer pathophysiology, the targeting of the TSHR offers a logical model for disease control. We review the structure and function of the TSHR and the progress in both small molecule ligands and TSHR antibodies for their therapeutic potential. Stabilization of a preferential conformation for the TSHR by allosteric ligands and TSHR antibodies with selective modulation of the signaling pathways is now possible. These tools may be the next generation of therapeutics for controlling the pathophysiological consequences mediated by the effects of the TSHR in the thyroid and other extrathyroidal tissues.

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Citations

Jan 21, 2016·Proceedings of the National Academy of Sciences of the United States of America·Pratik SaxenaMartin Fussenegger
Oct 7, 2015·Frontiers in Endocrinology·Selvaraj G NatarajaStephen S Palmer
Oct 13, 2016·Frontiers in Endocrinology·Rauf LatifTerry F Davies
Mar 30, 2017·Endocrine-related Cancer·Christopher W RoweRoger Smith
Dec 4, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Basil RapoportSandra M McLachlan
Oct 11, 2019·Current Opinion in Oncology·Stefania BulottaDiego Russo
Sep 2, 2016·Endocrinology·Paul M Yen
Jun 24, 2017·Journal of Endocrinological Investigation·M RossiF Giorgi
Oct 19, 2017·Frontiers in Endocrinology·Ramkumarie BaliramTerry F Davies
Jul 4, 2020·Nature Reviews. Disease Primers·Terry F DaviesGeorge J Kahaly
Feb 15, 2019·Frontiers in Endocrinology·Terry F Davies, Rauf Latif
Jan 23, 2019·Frontiers in Endocrinology·Simeng SunTerry F Davies
Jun 1, 2018·International Journal of Endocrinology·Nattakarn SuwansaksriTada Kunavisarut
May 9, 2021·Molecular and Cellular Endocrinology·Francesca Coscia, Ajda Taler-Verčič
Jan 30, 2021·European Thyroid Journal·Gerd KrauseRalf Schülein

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