Nicotinic 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 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.
The first medication to be administered orally to treat excessive cholesterol levels and to balance low density lipoproteins (LDL) and high density lipoproteins (HDL) was nicotinic acid (niacin). Surprisingly, the possible mechanism of action of this substance has just recently been clarified, in part due to the cloning of a G protein-coupled receptor (GPR109A). Both nicotinic acid and the ketone molecule β-hydroxybutyrate activate this receptor, but the latter is considered to be the more likely endogenous ligand for GPR109A.
Fig.1. Nicotinic acid related receptors. (Gille, 2008)
As a pioneer and the undisputed global leader in drug discovery, Creative Biolabs is confident in providing the domestic and international customers with the best possible nicotinic acid family related tools while at the most competitive price.
Overview of Nicotinic Acid Family
- HCAR2 (GPR109A)
It has been demonstrated that GPR109A couples to G proteins from the Gi family. Depending on the kind of cell, activation of Gi-type G proteins has distinct consequences on the cell. In adipocytes, the activity of receptors such as -adrenergic receptors that via activation of Gs boost adenylyl cyclase activity, increase cellular cAMP levels, and stimulate protein kinase A is countered by the nicotinic acid-induced suppression of adenylyl cyclase activity via GPR109A. (PKA). Hormone-sensitive lipase (HSL) and perilipin, which are necessary for triacylglycerol (TAG) hydrolysis, are two of the proteins that PKA phosphorylates. Phosphorylation of perilipin enables the now-activated HSL and another lipase, adipose triacylglycerol lipase (ATGL), to enter the lipid droplets holding TAGs and hydrolyze them into FFA and glycerol. Thus, activation of the Gi-coupled nicotinic acid receptor inhibits the cAMP/PKA signaling cascade, inhibiting lipolysis and the subsequent release of FFA into the circulation, so mediating the antilipolytic activity of nicotinic acid.
Fig.2. Multiple regulators of lipolysis in adipocytes. (Karpe & Frayn, 2004)
- HCAR3 (GPR109B)
GPR109B is the protein that is most similar to GPR109A. GPR109B and GPR109A are almost 96% identical to one another. In addition to a variation in 17 amino acids, mostly found in the first two extracellular loops, GPR109B differs from GPR109A by 24 amino acids at the carboxy terminus. Although findings indicate that the receptor is expressed in a way similar to GPR109A, a physiological significance for GPR109B has not yet been established. As a result, GPR109B could potentially serve as an alternate therapeutic target to GPR109A.
- HCAR1 (GPR81)
Additionally near GPR109A is GPR81. GPR81 is a receptor that is present in both rats and humans. It is almost exclusively expressed in adipose tissue, although its significance has not yet been established.
Nicotinic Acid Family Drug Discovery
The nicotinic acid receptor GPR109A, as well as its near relatives GPR109B and GPR81, are related to Gi-type G proteins and are largely expressed in adipocytes. In order to precisely control the regulation of lipolytic activity in adipose tissue, the receptors serve as metabolic sensors. Investigating the potential function of these receptors in metabolic diseases like obesity, dyslipidemia, and diabetes mellitus will be fascinating. As the recognized antidyslipidemic medication nicotinic acid is a GPR109A receptor, GPR109B and in particular GPR81 offer interesting therapeutic targets that may be more advantageous than GPR109A. To further assess these receptors as potential targets for fresh treatment approaches, the discovery of subtype-specific and more powerful ligands of this receptor family would be a crucial necessity.
References
- Gille, A.; et al. Nicotinic acid: pharmacological effects and mechanisms of action. Annu. Rev. Pharmacol. Toxicol. 2008, 48: 79-106.
- Karpe, F.; Frayn, K. N. The nicotinic acid receptor–a new mechanism for an old drug. The Lancet. 2004, 363(9424): 1892-1894.
