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Structure of the intact PPAR-γ–RXR-α nuclear receptor complex on DNA
TLDR
Structures of intact PPAR-γ and RXR-α are presented as a heterodimer bound to DNA, ligands and coactivator peptides, allowing the ligand-binding domain (LBD) of PPar-γ to contact multiple domains in both proteins.
Regulation of Circadian Behavior and Metabolism by Synthetic REV-ERB Agonists
TLDR
Treatment of diet-induced obese mice with a REV-ERB agonist decreased obesity by reducing fat mass and markedly improving dyslipidaemia and hyperglycaemia, indicating that synthetic REV -ERB ligands that pharmacologically target the circadian rhythm may be beneficial in the treatment of sleep disorders as well as metabolic diseases.
Suppression of TH17 Differentiation and Autoimmunity by a Synthetic ROR Ligand
TLDR
The data demonstrate the feasibility of targeting the orphan receptors RORα and RORγt to inhibit specifically TH17 cell differentiation and function, and indicate that this novel class of compound has potential utility in the treatment of autoimmune diseases.
The Benzenesulfoamide T0901317 [N-(2,2,2-Trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide] Is a Novel Retinoic Acid Receptor-Related Orphan
TLDR
The results demonstrate that small molecules can be used to target the RORs for therapeutic intervention in metabolic and immune disorders and an excellent starting point for the development of ROR selective modulators.
Identification of SR8278, a synthetic antagonist of the nuclear heme receptor REV-ERB.
TLDR
The identification of the first REV-ERB antagonist, SR8278, is reported, which is structurally similar to the agonist but blocks the ability of the GSK4112 to enhance REV -ERBα-dependent repression in a cotransfection assay.
DNA binding alters coactivator interaction surfaces of the intact VDR–RXR complex
TLDR
It is shown that binding of intact heterodimer to DNA alters the receptor dynamics in regions remote from the DNA-binding domains (DBDs), including the coactivator binding surfaces of both co-receptors, and that the sequence of the DNA response element can determine these dynamics.
Nuclear Receptors and Their Selective Pharmacologic Modulators
TLDR
The development and pharmacology of a range of selective nuclear receptor modulators are reviewed, where ligands display agonist/partial agonist-binding domain of nuclear receptors function in a tissue or gene selective manner.
Modulation of Retinoic Acid Receptor-related Orphan Receptor α and γ Activity by 7-Oxygenated Sterol Ligands*
TLDR
It is demonstrated that 7-oxygenated sterols function as high affinity ligands for both RORα and RORγ by directly binding to their ligand-binding domains, modulating coactivator binding, and suppressing the transcriptional activity of the receptors.
Characterization of the Core Mammalian Clock Component, NPAS2, as a REV-ERBα/RORα Target Gene*
TLDR
A mechanism by which RORα and REV-ERBα coordinately regulate the expression of the positive arm of the circadian rhythm feedback loop is suggested.
Regulation of Cholesterologenesis by the Oxysterol Receptor, LXRα*
TLDR
Examination of the CYP51A1 gene revealed that both the SRE and nLXRE are required for normal oxysterol-dependent repression of this gene, suggesting that LXRα plays an important role in the regulation of cholesterol biosynthesis.
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