Current Topics in Medicinal Chemistry - Volume 8, Issue 9, 2008

The human nuclear hormone receptor (NHR) family consists of 48 transcription regulators which, in turn, control a vast assortment of biological functions. Receptor activation occurs upon binding with a variety of both high- and low-affinity ligands including steroids, prostanoids, retinoids, Vitamin D, oxysterols and bile acids. Many of these receptors serve as the basis for clinical intervention and involve treatments for breas Read More

The Peroxisome Proliferator-Activated Receptors-PPARα, PPARγ, and PPARδ--are members of the nuclear receptor gene family that have emerged as therapeutic targets for the development of drugs to treat human metabolic diseases. The discovery of high affinity, subtype-selective agonists for each of the three PPAR subtypes has allowed elucidation of the pharmacology of these receptors and development of first-generatio Read More

Steroidal glucocorticoids are widely prescribed for the treatment of a variety of inflammatory and autoimmune diseases. Although they are effective, the side-effects associated with chronic glucocorticoid treatment, such as osteoporosis and hyperglycemia, can severely limit their long-term use. Hence, there is a need to develop new effective anti-inflammatory agents for systemic use which are dissociated from their u Read More

Synthetic steroidal progestins and antiprogestins have been widely used for decades to treat many gynecological conditions. The concept of selective progesterone receptor modulators (SPRMs) has been developed in recent years to design new therapeutic agents that have desirable PR modulating activity with significantly reduced sideeffects or increased safety margin. This review describes medicinal chemistry progres Read More

The Liver X Receptors LXRα and LXRβ are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. Seminal studies with genetic and chemical tools were instrumental in the elucidation of cholesterol metabolism, gluconeogenesis, inflammation, and lipogenesis as signaling pathways that are controlled by the LXRs. First generation non-steroidal LXR agonists show beneficial effects in Read More

Selective Estrogen Receptor Modulators (SERMs) have been the subject of extensive medicinal chemistry efforts at several pharmaceutical companies, including Merck. The Merck effort produced a wide variety of SERMs including ER-?? selective antagonists and ER-?? agonists in addition to balanced (non-selective) analogs. This article will provide a broad overview of the Merck SERM medicinal chemistry effort as publishe Read More

This review covers recent progress in the discovery of selective glucocorticoid receptor (GR) antagonists. Potential therapeutic applications of selective GR antagonists are described including the pharmacological rationale and, in some cases, clinical evidence that underlies these proposed uses. Disease areas that are discussed are Cushing's syndrome, psychotic depression, diabetes, obesity, Alzheimer's disease, neuropathi Read More

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