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Small-Molecule TSH Receptor Modulators for Diagnosis and Treatment of Thyroid Disease and Cancer

Posted May 03 2009 5:00pm

Description of Invention:
NIH investigators have discovered a series of low molecular weight thyroid-stimulating hormone (TSH) receptor modulators for use in evaluation and treatment of thyroid diseases, including thyroid cancer, hypothyroidism, and hyperthyroidism. Certain compounds encompassed by this technology are more potent and/or more specific TSH receptor activators than currently-available compounds; also, as small molecules, these compounds are orally available and are expected to be less costly and more straightforward to produce than recombinant protein counterparts currently on the market.

According to the National Cancer Institute, over 37,000 new cases of thyroid cancer were diagnosed in the United States in 2008, and over 1,500 people died of this disease. These numbers reflect a progressive increase in the incidence of thyroid cancer over the last several years. Because most cases of thyroid cancer are diagnosed in patients between the ages of 20 and 54, these patients will undergo decades of follow-up monitoring after cancer treatment. For the last decade, recombinant TSH protein has been used in this follow-up to increase detection sensitivity for recurrent or metastatic thyroid cancer, and to eliminate side effects associated with withdrawal of hormone replacement therapy. A small-molecule TSH receptor agonist encompassed by this technology would have utility similar to recombinant TSH, but would have several distinct advantages. For example, as a small molecule, rather than a recombinant protein, such a compound would be orally available, and would be less difficult and expensive to produce. These compounds are also more potent and/or specific for the TSH receptor than other known small-molecule TSH receptor agonists. In addition to use in thyroid cancer screening, these compounds may also be useful for adjunctive treatment (with radioactive iodide) of thyroid cancer, and certain forms of hypothyroidism.

Hyperthyroidism, or an overactive thyroid gland, affects about 1% of people in the United States and is often caused by autoimmune over-stimulation of the thyroid gland (Graves’ disease), or by thyroid tumors. Drugs currently used for treatment of hyperthyroidism inhibit synthesis of thyroid hormones; the TSH receptor antagonist compounds encompassed by this technology have the advantage of directly inhibiting activity of the TSH receptor, rather than inhibiting thyroid hormone synthesis.

  • Diagnostic tools for evaluation and treatment of thyroid cancer.
  • Therapeutics for thyroid cancer, hyperthyroidism, and hypothyroidism.

Development Status:
Early stage

Marvin C Gershengorn (NIDDK)

Patent Status:
HHS, Reference No. E-223-2006/1
US, Application No. 12/291,932 filed 14 Nov 2008
PCT, Application No. PCT/US2008/011958 filed 20 Oct 2008

National Phase entered in Australia, Canada, Europe, Japan, and the United States

Relevant Publication:
  1. S Moore, H Jaeschke, G Kleinau, S Neumann, S Costanzi, JK Jiang, J Childress, BM Raaka, A Colson, R Paschke, G Krause, CJ Thomas, MC Gershengorn. Evaluation of small-molecule modulators of the luteinizing hormone/choriogonadotropin and thyroid stimulating hormone receptors: structure-activity relationships and selective binding patterns. J Med Chem. 2006 Jun 29;49(13):3888-3896. [ PubMed abs ]
  2. S Neumann, G Kleinau, S Costanzi, S Moore, BM Raaka, CJ Thomas, G Krause, MC Gershengorn: A low molecular weight antagonist for the human thyrotropin receptor with therapeutic potential for hyperthyroidism. Endocrinology. 2008 31 Jul; published online ahead of print, doi:10.1210/en.2008-0836. [ [PubMed abs] ]
  3. Unpublished data are also available for review under a CDA.

Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The NIDDK Clinical Endocrinology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize small molecule TSH receptor modulators. Please contact Patricia Mello Lake; 301-451-3636; for more information.

Cancer - Diagnostics
Cancer - Therapeutics
Internal Medicine
Internal Medicine - Diagnostics
Internal Medicine - Therapeutics

For Additional Information Please Contact:
Tara Kirby Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-435-4426
Fax: 301-402-0220

Ref No: 1852

Updated: 05/2009

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