Manipulating Liver Bile Acid Signaling by Nanodelivery of Bile Acid Receptor Modulators for Liver Cancer Immunotherapy

Nano Letters ◽  
2021 ◽  
Author(s):  
Guofeng Ji ◽  
Xinghui Si ◽  
Si Dong ◽  
Yajun Xu ◽  
Mingqiang Li ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Cancer ◽  
Cancer Immunotherapy ◽  
Acid Receptor ◽  
Bile Acid Receptor ◽  
Receptor Modulators

scholarly journals Introduction of Nonacidic Side Chains on 6-Ethylcholane Scaffolds in the Identification of Potent Bile Acid Receptor Agonists with Improved Pharmacokinetic Properties

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1043 ◽  
Author(s):  
Claudia Finamore ◽  
Giuliana Baronissi ◽  
Silvia Marchianò ◽  
Francesco Di Leva ◽  
Adriana Carino ◽  
...  
Keyword(s):  
Bile Acid ◽  
Metabolic Disorders ◽  
Farnesoid X Receptor ◽  
Pharmacological Characterization ◽  
Acid Receptor ◽  
Pharmacokinetic Properties ◽  
Docking Calculations ◽  
Bile Acid Receptor ◽  
Receptor Modulators

As a cellular bile acid sensor, farnesoid X receptor (FXR) and the membrane G-coupled receptor (GPBAR1) participate in maintaining bile acid, lipid, and glucose homeostasis. To date, several selective and dual agonists have been developed as promising pharmacological approach to metabolic disorders, with most of them possessing an acidic conjugable function that might compromise their pharmacokinetic distribution. Here, guided by docking calculations, nonacidic 6-ethyl cholane derivatives have been prepared. In vitro pharmacological characterization resulted in the identification of bile acid receptor modulators with improved pharmacokinetic properties.

scholarly journals MiR-22-silenced Cyclin A Expression in Colon and Liver Cancer Cells Is Regulated by Bile Acid Receptor

2015 ◽  
Vol 290 (10) ◽  
pp. 6507-6515 ◽  
Author(s):  
Fan Yang ◽  
Ying Hu ◽  
Hui-Xin Liu ◽  
Yu-Jui Yvonne Wan
Keyword(s):  
Bile Acid ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Cyclin A ◽  
Acid Receptor ◽  
Liver Cancer Cells ◽  
Bile Acid Receptor

Characterization of a Structural Leoligin Analog as Farnesoid X Receptor Agonist and Modulator of Cholesterol Transport

Planta Medica ◽  
2020 ◽  
Vol 86 (15) ◽  
pp. 1097-1107
Author(s):  
Angela Ladurner ◽  
Thomas Linder ◽  
Limei Wang ◽  
Verena Hiebl ◽  
Daniela Schuster ◽  
...  
Keyword(s):  
Bile Acid ◽  
Target Genes ◽  
Pharmacophore Model ◽  
Farnesoid X Receptor ◽  
Model Systems ◽  
Cholesterol Transport ◽  
Peroxisome Proliferator ◽  
Acid Receptor ◽  
Bile Acid Receptor ◽  
Receptor Modulators

AbstractThe ligand-activated farnesoid X receptor is an emerging therapeutic target for the development of drugs against metabolic syndrome-related diseases. In this context, selective bile acid receptor modulators represent a novel concept for drug development. Selective bile acid receptor modulators act in a target gene- or tissue-specific way and are therefore considered less likely to elicit unwanted side effects. Based on leoligin, a lignan-type secondary plant metabolite from the alpine plant Leontopodium nivale ssp. alpinum, 168 synthesized structural analogs were screened in a farnesoid X receptor in silico pharmacophore-model. Fifty-six virtual hits were generated. These hits were tested in a cell-based farnesoid X receptor transactivation assay and yielded 7 farnesoid X receptor-activating compounds. The most active one being LT-141A, with an EC50 of 6 µM and an Emax of 4.1-fold. This analog did not activate the G protein-coupled bile acid receptor, TGR5, and the metabolic nuclear receptors retinoid X receptor α, liver X receptors α/β, and peroxisome proliferator-activated receptors β/γ. Investigation of different farnesoid X receptor target genes characterized LT-141A as selective bile acid receptor modulators. Functional studies revealed that LT-141A increased cholesterol efflux from THP-1-derived macrophages via enhanced ATP-binding cassette transporter 1 expression. Moreover, cholesterol uptake in differentiated Caco-2 cells was significantly decreased upon LT-141A treatment. In conclusion, the leoligin analog LT-141A selectively activates the nuclear receptor farnesoid X receptor and has an influence on cholesterol transport in 2 model systems.

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