Retinoid X Receptor Selective Agonists and their Synthetic Methods
| Autor: | Carl E. Wagner, Pamela A. Marshall, Michael C. Heck, Peter W. Jurutka |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pregnane X receptor Binding Sites Retinoid X receptor alpha Chemistry General Medicine Retinoid X receptor Retinoid X receptor gamma Cell biology Retinoids 03 medical and health sciences Liver X receptor beta Retinoic acid receptor Retinoid X Receptors 030104 developmental biology 0302 clinical medicine Biochemistry 030220 oncology & carcinogenesis Drug Discovery Constitutive androstane receptor Retinoid X receptor beta |
| Zdroj: | Current Topics in Medicinal Chemistry. 17:742-767 |
| ISSN: | 1568-0266 |
| DOI: | 10.2174/1568026616666160617091559 |
| Popis: | Since the isolation and identification of the retinoid X receptor (RXR) as a member of the nuclear receptor (NR) superfamily in 1990, its analysis has ushered in a new understanding of physiological regulation by nuclear receptors, and novel methods to identify other unknown and orphan receptors. Expression of one or more of the three isoforms of RXR-α, β, and γ-can be found in every human cell type. Biologically, RXR plays a critical role through its ability to partner with other nuclear receptors. RXR is able to regulate nutrient metabolism by forming "permissive" heterodimers with peroxisome proliferator-activated receptor (PPAR), liver-X-receptor (LXR), farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR), which function when ligands are bound to one or both of the heterodimer partners. Conversely, RXR is able to form "nonpermissive" heterodimers with vitamin D receptor (VDR), thyroid receptor (TR) and retinoic acid receptor (RAR), which function only in the presence of vitamin D, T3 and retinoic acid, respectively. Furthermore, RXR can form homodimers in the presence of a selective agonist, or rexinoid, to regulate gene expression and to either inhibit proliferation or induce apoptosis in human cancers. Thus, over the last 25 years there have been several reports on the design and synthesis of small molecule rexinoids. This review summarizes the synthetic methods for several of the most potent rexinoids thus far reported. |
| Databáze: | OpenAIRE |
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