IGF::OT::IGF LOW MOLECULAR WEIGHT TSH HORMONE RECEPTOR AGONIST FOR THYROID CANCER

Following ablative surgery for thyroid cancer, follow-up management of patients includes monitoring for radioiodine uptake or serum TG levels. Recombinant human thyroid stimulating hormone (rhTSH) is currently used to increase the sensitivity of measurements in patients on thyroid hormone replacement; however, rhTSH is expensive to produce and requires injection for delivery. A small-molecule thyroid stimulating hormone receptor (TSHR) agonist may offer the beneficial effects as rhTSH but at a lower cost and with oral administration. We propose here to evaluate Compound 1 (NCGC reference # 00161870-01) for its potential as a clinically translatable TSHR agonist. We propose three aims to: 1.) SyntheSize 50 grams of compound 1 and evaluate its effect onTSH receptors in cells, 2.) Determine pharmacokinetics in rats, and 3.) Identify a safe dose of compound 1 for pre-IND investigations. Also, we will evaluate the genotoxicity of this compound in rats. The successful completion of this phase I SBIR willallow compound 1 to be advanced to a phase II application to develop a new diagnostic for use in patients with thyroid cancer.