Current Topics in Medicinal Chemistry - Volume 3, Issue 14, 2003

Over the last several years, the nuclear hormone receptor superfamily has enjoyed a renaissance as a target of pharmaceutical research. These ligand-gated transcription factors regulate a plethora of biological activities and exert key roles in the pathophysiology of major disease states including diabetes, obesity, osteoporosis, inflammation, atherosclerosis, and congestive heart failure, just to name a few. The utilization Read More

The natural calcium-regulating hormone 1α,25-dihydroxyvitamin D3 (1,25D3) is a secosteroid that offers organic chemists many sites for modifying structural and / or functional groups. Such modifications alter the chemistry, stereochemistry, and biological properties of the natural hormone. The resulting deltanoids (vitamin D analogs) have been used in the past two decades as molecular probes to investigate structure-functi Read More

Small molecules such as retinoids, steroid hormones, fatty acids, cholesterol metabolites, or xenobiotics are involved in the regulation of numerous physiological and patho-physiological processes by binding to and controlling the activity of members of the nuclear receptor (NR) superfamily of transcription factors. In addition to natural ligands, synthetic agonists or antagonists have been identified that in some cases specifically Read More

Thyroid hormone regulates many important processes in vertebrates. Analysis of the symptoms that accompany hypo- and hyperthyroidism, the most common disorders of the thyroid, suggests that there are certain desirable biological effects brought about by an excess or deficiency of thyroid hormone, and that selective thyroid hormone receptor modulators (STRMs) would be potentially useful therapeutic agents. This r Read More

Glucocorticoids have a pervasive role in human health and physiology. The endogenous members of this family are involved in a breadth of endocrine functions including metabolism of lipids, carbohydrates and proteins, stress response, fluid and electrolyte balance, as well as maintenance of immunological, renal and skeletal homeostasis. The predominant mode of action of glucocorticoids involves regulation Read More

Nuclear hormone receptors are ligand-activated transcription factors that regulate gene expression and play a critical role in endocrine signaling. Orphan nuclear receptors belong to this gene super-family but their target genes and physiological function have not been completely elucidated. In recent years, the identification of natural ligands for these orphan receptors, their expression pattern in different tissues and studies Read More

As master regulators of lipid metabolism the peroxisome proliferator activated receptor (PPAR) family controls a wide variety of cellular processes, and thus it is not surprising that a large effort has focussed on discovering agents to pharmacologically modulate activity of these receptors. Early generation PPAR ligands, such as the fibrates and the thiazolidinediones (TZDs), were discovered empirically through an in vivo structure Read More

The estrogen receptor is a regulator of a wide range of physiological functions, including the female reproductive system, in addition to bone, cardiovascular and CNS function. ER ligands have been approved for the treatment of menopausal symptoms, breast cancer and osteoporosis, however the search continues for new modulators of ER function with improved properties. Progress in medicinal chemistry programs h Read More