Succinate 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 tricarboxylic acid (TCA) cycle intermediate succinate is essential for the production of adenosine triphosphate (ATP) in mitochondria. Increased expression of HIF-1α-dependent genes results in rapid ATP synthesis and activation of the pentose-phosphate pathway. The capacity of the activated cell for biosynthesis is increased by these occurrences. Succinate levels were found to be higher in some tumors, which caused HIF-1α to stabilize. Succinate was demonstrated to directly block the prolyl hydroxylase domain (PHD) enzyme activity in macrophages, simulating its actions in tumors. This led to the stability of HIF-1𝜶 and the activation of a number of target genes.
Fig.1. Parallels between macrophages in relation to succinate. (Mills & O’Neill, 2014)
Creative Biolabs can offer succinate family in vitro assays and related tools to contribute to the success of drug discovery:
Overview of Succinate Family
- SUCNR1
Succinate acts as the SUCNR1's ligand in inflammatory conditions. This suggests that succinate's signaling functions go beyond only stabilizing HIF-1α. Mouse kidney, liver, spleen, small intestine, and DCs all have significant levels of SUCNR1 expression. It has only recently been clear that SUCNR1 activates a signaling cascade. When succinate was used to activate human embryonic kidney 293 cells that had been engineered to express SUCNR1, inositol trisphosphate (IP3) buildup, calcium mobilization, and extracellular signal-regulated kinase (ERK) activation occurred in a manner reminiscent of the Gi and Gq signaling cascades. In fact, succinate-induced responses were hampered by the application of the respective inhibitors of Gq and Gi signaling, YM254890 and pertussis toxin. Following succinate-stimulated SUCNR1 activation, calcium-dependent NO and prostaglandin E2 (PGE2) synthesis was also noted. Succinate stimulates calcium mobilization and ERK1/2 phosphorylation in human monocyte-derived DCs (MoDCs) as well as HEK293 cells, indicating that SUCNR1 signaling is also active in immune cells.
Fig.2. Signaling pathways of SUCNR1. (Gilissen, 2016)
Succinate Family Drug Discovery
There is potential for developing new pharmacological methods for succinate-mediated regulation given the significant regulatory roles that succinate plays in lipid metabolism, blood cell and vessel formation, the regulation of blood pressure and the cardiovascular system, and immune responses. Finding SUCNR1 receptor agonists and antagonists as possible drugs for the pharmacotherapy of hypoxic illnesses, renal hypertension, diabetic lesions, metabolic syndrome, autoimmune diseases, etc., is of great interest. The development of fundamentally novel pharmaceutical approaches for the prevention and treatment of these disorders will be possible with a better understanding of the mechanisms governing and modulating metabolic activities in health and pathology.
References
- Mills, E.; O’Neill, L.A. Succinate: a metabolic signal in inflammation. Trends in cell biology. 2014, 24(5): 313-320.
- Gilissen, J.; et al. Insight into SUCNR1 (GPR91) structure and function. Pharmacology & therapeutics. 2016, 159: 56-65.
