Discovery of 2H-chromone-4-one based sulfonamide derivatives as potent retinoic acid receptor-related orphan receptor γt inverse agonists

2021 ◽  
pp. 114065
Author(s):  
Lei Chen ◽  
Mei Su ◽  
Xian-Zhi Wu ◽  
De-Zhong Wang ◽  
Yang-yang Kang ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Orphan Receptor ◽  
Inverse Agonists ◽  
Acid Receptor

scholarly journals Ligand-Based Design of Allosteric Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) Inverse Agonists

2019 ◽  
Vol 63 (1) ◽  
pp. 241-259 ◽  
Author(s):  
Femke A. Meijer ◽  
Richard G. Doveston ◽  
Rens M.J.M. de Vries ◽  
Gaël M. Vos ◽  
Alex A.A. Vos ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Orphan Receptor ◽  
Inverse Agonists ◽  
Acid Receptor

scholarly journals Discovery of Potent and Orally Bioavailable Inverse Agonists of the Retinoic Acid Receptor-Related Orphan Receptor C2

2019 ◽  
Vol 10 (6) ◽  
pp. 972-977 ◽  
Author(s):  
Stefan von Berg ◽  
Yafeng Xue ◽  
Mia Collins ◽  
Antonio Llinas ◽  
Roine I. Olsson ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Orphan Receptor ◽  
Inverse Agonists ◽  
Acid Receptor ◽  
Orally Bioavailable

scholarly journals Hepatocyte nuclear factor-6 stimulates transcription of the alpha-fetoprotein gene and synergizes with the retinoic-acid-receptor-related orphan receptor alpha-4

2003 ◽  
Vol 369 (3) ◽  
pp. 583-591 ◽  
Author(s):  
Habib NACER-CHERIF ◽  
Brigitte BOIS-JOYEUX ◽  
Guy G. ROUSSEAU ◽  
Frédéric P. LEMAIGRE ◽  
Jean-Louis DANAN
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Orphan Receptor ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Acid Receptor ◽  
Splicing Isoforms ◽  
Liver Gene ◽  
A Site ◽  
Putative Binding Site

The rat α-fetoprotein (afp) gene is controlled by three enhancers whose function depends on their interaction with liver-enriched transcription factors. The afp enhancer III, located at −6kb, is composed of three regions that act in synergy. Two of these regions, called s1 and s2, contain a putative binding site for hepatocyte nuclear factor-6 (HNF-6). This factor is the prototype of the ONECUT family of cut-homoeodomain proteins and is a known regulator of liver gene expression in adults and during development. We show here that the two splicing isoforms of HNF-6 bind to a site in the s1 region and in the s2 region. The core sequence of the s1 site corresponds to none of the known HNF-6 binding sites. Nevertheless, the binding properties of the s1 site are identical with those of the s2 site and of previously characterized HNF-6 binding sequences. The HNF-6 consensus should therefore be rewritten as DRRTCVATND. Binding of HNF-6 to the s1 and s2 sites requires both the cut and the homoeo domains, is co-operative and induces DNA bending. HNF-6 strongly stimulates the activity of the afp enhancer III in transient transfection experiments. This effect requires the stereo-specific alignment of the two HNF-6 sites. Moreover, HNF-6 stimulates the enhancer in synergy with the retinoic-acid-receptor-related orphan receptor α (RORα), which binds to a neighbouring site in the s1 region. Thus expression of the afp gene requires functional interactions between HNF-6 molecules and between HNF-6 and RORα.

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