Retinoid X Receptor Antagonists

Retinoid X receptor (RXR) antagonists are not only useful as chemical tools for biological research, but are also candidate drugs for the treatment of various diseases, including diabetes and allergies, although no RXR antagonist has yet been approved for clinical use. In this review, we present a brief overview of RXR structure, function, and target genes, and describe currently available RXR antagonists, their structural classification, and their evaluation, focusing on the latest research.

• Publication year

  2018

• Venue

  International Journal of Molecular Sciences

• Publication date

  2018-06-13

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.3390/ijms19082354PMID 30103423PMCID 6121510
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Characterization and comparison of transcriptional activities of the retinoid X receptors by various organotin compounds in three prosobranch gastropods; Thais clavigera, Nucella lapillus and Babylonia japonica.

  2018cited by this paper
• RXR Ligands Modulate Thyroid Hormone Signaling Competence in Young Xenopus laevis Tadpoles

  2018cited by this paper
• RXR Ligands Negatively Regulate Thrombosis and Hemostasis

  2017cited by this paper
• TRC4, an improved triptolide derivative, specifically targets to truncated form of retinoid X receptor‐alpha in cancer cells

  2017cited by this paper
• Human stem cell-derived hepatocytes as a model for hepatitis B virus infection, spreading and virus-host interactions.

  2017cited by this paper
• The unexpected teratogenicity of RXR antagonist UVI3003 via activation of PPAR&ggr; in Xenopus tropicalis

  2017influential reference
• Virtual screening and experimental validation identify novel modulators of nuclear receptor RXRα from Drugbank database.

  2017cited by this paper
• TSLP expression in the skin is mediated via RARγ-RXR pathways.

  2016cited by this paper
• Protective effects of retinoid x receptors on retina pigment epithelium cells.

  2016cited by this paper
• Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination.

  2015cited by this paper
• Tributyltin engages multiple nuclear receptor pathways and suppresses osteogenesis in bone marrow multipotent stromal cells.

  2015cited by this paper
• RXR partial agonist produced by side chain repositioning of alkoxy RXR full agonist retains antitype 2 diabetes activity without the adverse effects.

  2015cited by this paper
• Structural Basis of Natural Promoter Recognition by the Retinoid X Nuclear Receptor

  2015cited by this paper
• Nitrostyrene Derivatives Act as RXRα Ligands to Inhibit TNFα Activation of NF-κB.

  2015cited by this paper
• NSC-640358 acts as RXRα ligand to promote TNFα-mediated apoptosis of cancer cell

  2015cited by this paper
• Quantitative toxicoproteomic analysis of zebrafish embryos exposed to a retinoid X receptor antagonist UVI3003

  2015influential reference
• A representative retinoid X receptor antagonist UVI3003 induced teratogenesis in zebrafish embryos

  2015influential reference
• The Crucial Involvement of Retinoid X Receptors in DDE Neurotoxicity

  2015cited by this paper
• Effects of antagonist of retinoid X receptor (UVI3003) on morphology and gene profile of Xenopus tropicalis embryos.

  2014cited by this paper
• Sulindac-derived RXRα modulators inhibit cancer cell growth by binding to a novel site.

  2014cited by this paper
• An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro

  2014cited by this paper
• Apoptotic and neurotoxic actions of 4-para-nonylphenol are accompanied by activation of retinoid X receptor and impairment of classical estrogen receptor signaling.

  2014cited by this paper
• Regulation of the nongenomic actions of retinoid X receptor-α by targeting the coregulator-binding sites

  2014cited by this paper
• Identification of a New RXRα Antagonist Targeting the Coregulator-Binding Site

  2014cited by this paper
• Protective role of retinoid X receptor in H9c2 cardiomyocytes from hypoxia/reoxygenation injury in rats.

  2014cited by this paper
• Structure of the retinoid X receptor α–liver X receptor β (RXRα–LXRβ) heterodimer on DNA

  2014cited by this paper
• Protective role of retinoid X receptor in H9c2 cardiomyocytes from hypoxia/reoxygenation injury in rats

  2014cited by this paper
• β-Apo-13-carotenone Regulates Retinoid X Receptor Transcriptional Activity through Tetramerization of the Receptor*

  2013cited by this paper
• Targeting truncated retinoid X receptor-α by CF31 induces TNF-α-dependent apoptosis.

  2013cited by this paper
• Nuclear Receptors and Their Selective Pharmacologic Modulators

  2013influential reference
• Regulation of microglia activation and deactivation by nuclear receptors

  2013cited by this paper
• Synthesis and SAR study of modulators inhibiting tRXRα-dependent AKT activation.

  2013influential reference
• Retinoid X receptors in macrophage biology.

  2013cited by this paper
• Regulation of proteolytic cleavage of retinoid X receptor-α by GSK-3β.

  2013cited by this paper
• Bone marrow NR4A expression is not a dominant factor in the development of atherosclerosis or macrophage polarization in mice[S]

  2013influential reference
• Role of bexarotene in the treatment of cutaneous T-cell lymphoma: the clinical and immunological sides.

  2013cited by this paper
• Elevated COX2 expression and PGE2 production by downregulation of RXRα in senescent macrophages.

  2013cited by this paper
• Modulation of RXR function through ligand design.

  2012cited by this paper
• Nur77turing macrophages in atherosclerosis.

  2012cited by this paper
• Antagonist Effect of Triptolide on AKT Activation by Truncated Retinoid X Receptor-alpha

  2012cited by this paper
• NR4A1 (Nur77) Deletion Polarizes Macrophages Toward an Inflammatory Phenotype and Increases Atherosclerosis

  2012cited by this paper
• Nuclear hormone receptors enable macrophages and dendritic cells to sense their lipid environment and shape their immune response.

  2012cited by this paper
• Structural Basis for Retinoic X Receptor Repression on the Tetramer*

  2011cited by this paper
• Discovery of a Potent Retinoid X Receptor Antagonist Structurally Closely Related to RXR Agonist NEt-3IB.

  2011cited by this paper
• Inhibition of mammary carcinoma cell growth by RXR is mediated by the receptor's oligomeric switch.

  2010cited by this paper
• NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling.

  2010cited by this paper
• The PXR is a drug target for chronic inflammatory liver disease

  2010influential reference
• Research Resource: Transcriptome Profiling of Genes Regulated by RXR and Its Permissive and Nonpermissive Partners in Differentiating Monocyte-Derived Dendritic Cells

  2010cited by this paper
• Modification at the acidic domain of RXR agonists has little effect on permissive RXR-heterodimer activation.

  2010cited by this paper
• Danthron Functions as a Retinoic X Receptor Antagonist by Stabilizing Tetramers of the Receptor*

  2010cited by this paper
• The “Phantom Effect” of the Rexinoid LG100754: Structural and Functional Insights

  2010cited by this paper
• Cell-Specific Interaction of Retinoic Acid Receptors with Target Genes in Mouse Embryonic Fibroblasts and Embryonic Stem Cells

  2009cited by this paper
• Modulating retinoid X receptor with a series of (E)-3-[4-hydroxy-3-(3-alkoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)phenyl]acrylic acids and their 4-alkoxy isomers.

  2009cited by this paper
• The effect of antagonists on the conformational exchange of the retinoid X receptor alpha ligand‐binding domain

  2009cited by this paper
• The Bile Acid Receptor FXR Is a Modulator of Intestinal Innate Immunity1

  2009cited by this paper
• Replacing alkyl sulfonamide with aromatic sulfonamide in sulfonamide-type RXR agonists favors switch towards antagonist activity.

  2009cited by this paper
• Reduction of Lipophilicity at the Lipophilic Domain of RXR Agonists Enables Production of Subtype Preference: RXRα‐Preferential Agonist Possessing a Sulfonamide Moiety

  2008cited by this paper
• Structure of the intact PPAR-γ–RXR-α nuclear receptor complex on DNA

  2008cited by this paper
• The First Potent Subtype‐Selective Retinoid X Receptor (RXR) Agonist Possessing a 3‐Isopropoxy‐4‐isopropylphenylamino Moiety, NEt‐3IP (RXRα/β‐dual agonist)

  2008cited by this paper
• Synthesis and structure-activity relationship of RXR antagonists based on the diazepinylbenzoic acid structure.

  2007cited by this paper
• Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function

  2007cited by this paper
• Synthesis and structure-activity relationship of novel RXR antagonists: orally active anti-diabetic and anti-obesity agents.

  2007cited by this paper
• Overview of Nomenclature of Nuclear Receptors

  2006influential reference
• International Union of Pharmacology. LXIII. Retinoid X Receptors

  2006cited by this paper
• Cutting Edge: Inhibition of the Retinoid X Receptor (RXR) Blocks T Helper 2 Differentiation and Prevents Allergic Lung Inflammation

  2006cited by this paper
• A retinoid X receptor antagonist, HX531, improves leptin resistance without increasing plasma leptin level in KK-Ay mice under normal dietary conditions.

  2005cited by this paper
• The R-enantiomer of the nonsteroidal antiinflammatory drug etodolac binds retinoid X receptor and induces tumor-selective apoptosis.

  2005influential reference
• Determinants of retinoid X receptor transcriptional antagonism.

  2004cited by this paper
• Nuclear receptor signaling in macrophages.

  2004influential reference
• Novel retinoid X receptor (RXR) antagonists having a dicarba-closo-dodecaborane as a hydrophobic moiety.

  2004cited by this paper
• DNA recognition by nuclear receptors.

  2004cited by this paper
• DNA-looping by RXR tetramers permits transcriptional regulation "at a distance".

  2004cited by this paper
• Design, synthesis and structure-activity relationship of novel RXR-selective modulators.

  2004influential reference
• In vivo activation of PPAR target genes by RXR homodimers

  2004cited by this paper
• Novel (2E,4E,6Z)-7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta-2,4,6-trienoic acid retinoid X receptor modulators are active in models of type 2 diabetes.

  2003influential reference
• Novel retinoid X receptor antagonists: specific inhibition of retinoid synergism in RXR-RAR heterodimer actions.

  2002cited by this paper
• The Human Estrogen Receptor-α Is a Ubiquitinated Protein Whose Stability Is Affected Differentially by Agonists, Antagonists, and Selective Estrogen Receptor Modulators*

  2001cited by this paper
• Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes.

  2001influential reference
• The rexinoid LG100754 is a novel RXR:PPARgamma agonist and decreases glucose levels in vivo.

  2001influential reference
• Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes.

  2001cited by this paper
• Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications.

  2000cited by this paper
• Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription.

  2000cited by this paper
• Role of LXRs in control of lipogenesis.

  2000cited by this paper
• sp2-bridged diaryl retinoids: effects of bridge-region substitution on retinoid X receptor (RXR) selectivity.

  2000cited by this paper
• Retinoid X receptor-antagonistic diazepinylbenzoic acids.

  1999influential reference
• A unified nomenclature system for the nuclear receptor superfamily

  1999cited by this paper
• The CoRNR motif controls the recruitment of corepressors by nuclear hormone receptors

  1999cited by this paper
• A unified nomenclature system for the nuclear receptor superfamily.

  1999cited by this paper
• Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors

  1997cited by this paper
• The phantom ligand effect: allosteric control of transcription by the retinoid X receptor.

  1997cited by this paper
• Identification, Characterization, and Tissue Distribution of Human Peroxisome Proliferator-activated Receptor (PPAR) Isoforms PPARγ2 versus PPARγ1 and Activation with Retinoid X Receptor Agonists and Antagonists*

  1997cited by this paper
• Activation of specific RXR heterodimers by an antagonist of RXR homodimers

  1996influential reference
• Identification of the first retinoid X, receptor homodimer antagonist.

  1996cited by this paper
• The role of general initiation factors in transcription by RNA polymerase II.

  1996cited by this paper
• Retinoid X receptor alpha forms tetramers in solution.

  1995cited by this paper
• Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-α

  1995cited by this paper
• The RXR heterodimers and orphan receptors.

  1995cited by this paper
• The nuclear receptor superfamily: the second decade.

  1995cited by this paper
• Unique response pathways are established by allosteric interactions among nuclear hormone receptors.

  1995influential reference
• Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids.

  1994cited by this paper

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  2025cites this paper
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  2024cites this paper
• Harnessing nuclear receptors to modulate hepatic stellate cell activation for liver fibrosis resolution.

  2024cites this paper
• Tuning RXR Modulators for PGC1α Recruitment.

  2024cites this paper
• Regulatory Non-Coding RNAs during Porcine Viral Infections: Potential Targets for Antiviral Therapy

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• Quantum Mechanical-Cluster Approach to Solve the Bioisosteric Replacement Problem in Drug Design

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• Neocryptotanshinone ameliorates insufficient energy production in heart failure by targeting retinoid X receptor alpha.

  2023cites this paper
• γ-Linolenic acid in maternal milk drives cardiac metabolic maturation

  2023cites this paper
• RXR signaling targeted cancer therapy

  2023cites this paper
• Direct evaluation of polarity of the ligand binding pocket in retinoid X receptor using a fluorescent solvatochromic agonist.

  2023cites this paper
• Retinoid X receptor agonists as selective modulators of the immune system for the treatment of cancer.

  2023cites this paper
• Cancer drugs with high repositioning potential for Alzheimer’s disease

  2023cites this paper
• Increased Molecular Flexibility Widens the Gap between K i and K d values in Screening for Retinoid X Receptor Modulators.

  2022cites this paper
• Rational Design of a New RXR Agonist Scaffold Enabling Single-Subtype Preference for RXRα, RXRβ, and RXRγ.

  2022cites this paper
• TLR4 Blockade Using Docosahexaenoic Acid Restores Vulnerability of Drug-Tolerant Tumor Cells and Prevents Breast Cancer Metastasis and Postsurgical Relapse

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• Design, synthesis and biological evaluation of acyl hydrazones-based derivatives as RXRα-targeted anti-mitotic agents.

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  2021cites this paper
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  2021cites this paper
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  2021cites this paper
• The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats

  2020cites this paper
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  2020cites this paper
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  2020cites this paper
• Discovery of a "Gatekeeper" Antagonist that Blocks Entry Pathway to Retinoid X Receptors (RXRs) without Allosteric Ligand Inhibition in Permissive RXR Heterodimers.

  2020cites this paper
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  2019cites this paper