Discovery and development of small molecule allosteric modulators of glycoprotein hormone receptors

作者：Nataraja Selvaraj G; Yu Henry N; Palmer Stephen S

来源：Frontiers in Endocrinology, 2015, 6: 142.

DOI：10.3389/fendo.2015.00142

• small molecule allosteric modulators
• follicle-stimulating hormone
• leutinizing hormone/chorionic gonadotropin
• thyroid-stimulating hormone
• G protein-coupled receptor
• glycoprotein hormone receptors
• leucine-rich repeat

Glycoprotein hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH) are heterodimeric proteins with a common α-subunit and hormone-specific β-subunit. These hormones are dominant regulators of reproduction and metabolic processes. Receptors for the glycoprotein hormones belong to the family of G protein-coupled receptors. FSH receptor (FSHR) and LH receptor are primarily expressed in somatic cells in ovary and testis to promote egg and sperm production in women and men, respectively. TSH receptor is expressed in thyroid cells and regulates the secretion of T3 and T4. Glycoprotein hormones bind to the large extracellular domain of the receptor and cause a conformational change in the receptor that leads to activation of more than one intracellular signaling pathway. Several small molecules have been described to activate/inhibit glycoprotein hormone receptors through allosteric sites of the receptor. Small molecule allosteric modulators have the potential ...

• 出版日期2015-9-14