Mini Reviews in Medicinal Chemistry - Volume 5, Issue 8, 2005

Nuclear receptor (NR) proteins are ligand-dependent transcription factors that belong to the superfamily of steroid/thyroid/retinoid/vitamin D receptors. NR family members play important roles in cell growth, differentiation, homeostasis, metabolism and development. NRs are modular proteins that contain three distinct functional domains. An Nterminal domain containing a ligand-independent activation function, AF-1, Read More

The nuclear receptor for progesterone is a target for contraception and for several therapeutic indications. Progestin agonists and antagonists in clinical use mimic the steroidal backbone of the cognate ligand, progesterone. Thus, they have significant cross-reactivity with other steroid receptors. Recently, nonsteroidal progesterone receptor ligands have begun to appear in the literature. This review will describe the cur Read More

Mineralocorticoid receptor (MR) antagonism has proven to effectively attenuate the pathophysiological effects of aldosterone in clinical and experimental settings of hypertension and heart failure. MR activates transcription of target genes upon aldosterone binding, and eplerenone selectively binds to MR and blocks aldosterone- mediated activation. In this review, we summarize the preclinical and clinical evidence s Read More

The farnesoid X receptor (FXR) is a nuclear receptor expressed in tissues exposed to high concentrations of bile acids such as the liver, kidney and intestine and functions as a bile acid sensor. FXR regulates the expression of various transport proteins and biosynthetic enzymes crucial to the physiological maintenance of lipids, cholesterol and bile acid homeostasis. The concept of reverse endocrinology, whereby the receptor Read More

Liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily of ligandactivated transcription factors. Two LXRs (LXRa and LXRb) were initially characterized as orphan members of this superfamily with disparate patterns of tissue expression. These two receptors later were recognized as sterol-responsive with the ability to directly bind several oxysterol metabolites. Many LXR target genes have been id Read More

Peroxisome proliferator-activated receptors (PPARs) alpha, gamma and delta (beta) are ligandactivated transcription factors of the nuclear hormone receptor superfamily which have been shown to play key roles in maintaining glucose and lipid homeostasis. The physiological effects of several marketed drugs for the treatment of dyslipidemia (fenofibrate and gemfibrozil) and diabetes (rosiglitazone and pioglitazone) hav Read More

Retinoids have shown beneficial therapeutic effects in pre-clinical and animal models for multiple pathologic indications, however severe adverse effects, restricting dosage and efficacy of oral formulations limit their use in patients. The focus of this review includes the actual medicinal use of retinoids and chemical efforts to generate highly selective and less toxic synthetic retinoids.

1α, 25-dihydroxyvitamin D3 {1,25-(OH)2D3}, the biologically active form of vitamin D, is an important hormone that is critically required for the maintenance of mineral homeostasis and structural integrity of bones. 1,25-(OH)2D3 accomplishes this by facilitating calcium absorption from the gut and by a direct action on osteoblasts, the bone forming cells. Apart form its classical actions on the gut and bone, 1,25- (OH)2D3 an Read More