Bile Acid Family Related Drug Discovery Products
Creative Biolabs has the assays you can rely on for high throughput screening, lead optimization, characterizing and discovering targets, and uncovering the complexity of disease pathways. We can offer membrane protein in vitro assay kits that save valuable laboratory time and is ideal for high throughput screening.
Membrane protein stable cell lines are widely used in many areas of biomedical research. Creative Biolabs can offer membrane protein stable cell lines to stablish in vitro models for High Throughput Screening.
Creative Biolabs' membrane preparations are useful for membrane protein research. We offer membrane preparations to study the role of membrane proteins in diseases. Membrane preparations from Creative Biolabs are quality-assured frozen membranes from cells expressing recombinant or natural receptors.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
As a bile acid (BA) membrane receptor, GPBAR1 controls the equilibrium of bile acids, the homeostasis of energy, and the metabolism of glucose. It belongs to the family of Gprotein-coupled receptors (GPCRs), which have seven transmembrane domains and use heterotrimeric G proteins to transmit extracellular signals. A detrimental regulator of NF-B-mediated liver inflammation is GPBAR1. In order to cause inflammation in the stomach, Helicobacter pylori infection upregulates the NF-B pathway. Cancer frequently develops as a result of chronic inflammation. The abnormal activation of NF-B signaling can be disrupted to significantly slow the growth of tumors.
Fig.1 The role of GPBAR1 in cholestatic diseases. (Zhang, 2022)
Creative Biolabs offers bile acid family drug discovery assays and products to help research groups accelerate drug discovery and development projects:
Overview of Bile Acid Receptor
The epithelial cells of the gallbladder and bile ducts, brown adipose tissue, muscle, intestine, kidney, placenta, and brain all have significant levels of GPBAR1 expression. Sinusoidal endothelial cells, bile duct epithelial cells, and Kupffer cells in the liver all express GPBAR1, but hepatocytes do not. Although (un)conjugated deoxycholic acid, CDCA, UDCA, and cholic acid also have an effect on GPBAR1, LCA is the most potent natural agonist of GPBAR1. Adenylate cyclase is stimulated by ligand binding to GPBAR1, which raises cAMP levels and stimulates adenylate cyclase, which then activates protein kinase A and starts additional downstream signaling processes. Through the inhibition of nuclear factor κB translocation, which lowers the production of proinflammatory cytokines and mediators as well as inducible nitric oxide synthase, activation of GPBAR1 exerts anti-inflammatory effects. Glucagon-like peptide 1 (GLP-1) is secreted by enteroendocrine cells after GPBAR1 activation. This incretin enhances insulin sensitivity, insulin secretion, and pancreatic function.
Fig.2 GPBAR1-expressing tissues and targets. (Schaap, 2014)
Bile Acid Receptor Drug Discovery
- Liver inflammation
Although the origin of cholestasis has been extensively researched, it is still unknown how BA damages the liver. BA's proinflammatory actions are what really damage the liver during cholestasis since BA activates the hepatocytes' signaling pathway and raises the production of proinflammatory mediators.
- Metabolism and inflammation
Following meal ingestion, the microbiota transforms polysaccharides into short-chain fatty acids, amino acids, and metabolites that the host can use to produce energy. BAs are a group of significant metabolites created by microorganisms and are of the most prevalent metabolites in the intestine. They are produced from cholesterol in the liver and further processed by the gut microbiota.
References
- Zhang, F.; et al. Therapeutic opportunities of GPBAR1 in cholestatic diseases. Frontiers in Pharmacology. 2022, 12: 4061.
- Schaap, F.G.; et al. Bile acid receptors as targets for drug development. Nature reviews Gastroenterology & hepatology. 2014, 11(1): 55-67.
