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A Low-Molecular-Weight Antagonist for the Human Thyrotropin Receptor with Therapeutic Potential for Hyperthyroidism

  1. Neumann, Susanne
  2. Kleinau, Gunnar
  3. Costanzi, Stefano
  4. Moore, Susanna
  5. Jiang, Jian-kang
  6. Raaka, Bruce M.
  7. Thomas, Craig J.
  8. Krause, Gerd
  9. Gershengorn, Marvin C.

WeightNameValue
1000 Titel
  • A Low-Molecular-Weight Antagonist for the Human Thyrotropin Receptor with Therapeutic Potential for Hyperthyroidism
1000 Autor/in
  1. Neumann, Susanne |
  2. Kleinau, Gunnar |
  3. Costanzi, Stefano |
  4. Moore, Susanna |
  5. Jiang, Jian-kang |
  6. Raaka, Bruce M. |
  7. Thomas, Craig J. |
  8. Krause, Gerd |
  9. Gershengorn, Marvin C. |
1000 Erscheinungsjahr 2008
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2008-07-31
1000 Erschienen in
1000 Quellenangabe
  • 149(12): 5945–5950
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613050/ |
  • https://doi.org/10.1210/en.2008-0836 |
1000 Ergänzendes Material
  • https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2008-0836#supplementary-data |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Low-molecular-weight (LMW) antagonists for TSH receptor (TSHR) may have therapeutic potential as orally active drugs to block stimulating antibodies (TsAbs) in Graves’ hyperthyroidism. We describe an approach to identify LMW ligands for TSHR based on Org41841, a LMW partial agonist for the LH/choriogonadotropin receptor and TSHR. We used molecular modeling and functional experiments to guide the chemical modification of Org41841. We identified an antagonist (NIDDK/CEB-52) that selectively inhibits activation of TSHR by both TSH and TsAbs. Whereas initially characterized in cultured cells overexpressing TSHRs, the antagonist was also active under more physiologically relevant conditions in primary cultures of human thyrocytes expressing endogenous TSHRs in which it inhibited TSH- and TsAb-induced up-regulation of mRNA transcripts for thyroperoxidase. Our results establish this LMW compound as a lead for the development of higher potency antagonists and serve as proof of principle that LMW ligands that target TSHR could serve as drugs in patients with Graves’ disease.
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/TmV1bWFubiwgU3VzYW5uZQ==|https://frl.publisso.de/adhoc/creator/S2xlaW5hdSwgR3VubmFy|https://frl.publisso.de/adhoc/creator/Q29zdGFuemksIFN0ZWZhbm8=|https://frl.publisso.de/adhoc/creator/TW9vcmUsIFN1c2FubmE=|https://frl.publisso.de/adhoc/creator/SmlhbmcsIEppYW4ta2FuZw==|https://frl.publisso.de/adhoc/creator/UmFha2EsIEJydWNlIE0u|https://frl.publisso.de/adhoc/creator/VGhvbWFzLCBDcmFpZyBKLg==|https://frl.publisso.de/adhoc/creator/S3JhdXNlLCBHZXJk|https://frl.publisso.de/adhoc/creator/R2Vyc2hlbmdvcm4sIE1hcnZpbiBDLg==
1000 Label
1000 Förderer
  1. National Institute of Diabetes and Digestive and Kidney Diseases |
  2. National Human Genome Research Institute |
  3. National Institutes of Health |
1000 Fördernummer
  1. -
  2. -
  3. -
1000 Förderprogramm
  1. Intramural Research Program
  2. Intramural Research Program
  3. Intramural Research Program
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer National Institute of Diabetes and Digestive and Kidney Diseases |
    1000 Förderprogramm Intramural Research Program
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer National Human Genome Research Institute |
    1000 Förderprogramm Intramural Research Program
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer National Institutes of Health |
    1000 Förderprogramm Intramural Research Program
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6405324.rdf
1000 Erstellt am 2017-11-07T16:19:58.013+0100
1000 Erstellt von 25
1000 beschreibt frl:6405324
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet Wed Aug 17 08:44:19 CEST 2022
1000 Objekt bearb. Wed Aug 17 08:44:19 CEST 2022
1000 Vgl. frl:6405324
1000 Oai Id
  1. oai:frl.publisso.de:frl:6405324 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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