Melanocortin 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 melanocortins refers to a class of structurally similar peptides that have melanotropic and corticotropic effects. Adrenocorticotropic hormone (ACTH), α-melanocyte stimulating hormone (MSH), β-MSH, and γ-MSH are the four melanocortins and are all derived from pro-opiomelanocortin (POMC). Proconvertases 1 and 2 are the two major proteolytic enzymes involved in the tissue-specific conversion of POMC into its numerous derivatives. Whereas proconvertase 1 produces ACTH and β-LPH, proconvertase 2 breaks down ACTH to produce α-MSH and β-endorphin.
Creative Biolabs can provide a wide variety of melanocortin family related tools for our clients to contribute to the success of your project:
Overview of Melanocortin Family
MCH, a natural ligand, binds to MCHR1 and couples to the proteins Gi, Go, and Gq. Hence, activation of MCHR1 results in increased intracellular Ca2+ accumulation via the Gq-coupled pathway and decreased levels of cyclic adenosine monophosphate (cAMP) via the Gi/o-coupled pathway. Further research on the MCHR1 signaling in recombinant cell lines and in brain slices shows that MCHR1 activation also results in ERK phosphorylation. MCH quickly generated a three- to fivefold increase in MAPK pathway activity in 3T3-L1 adipocytes.
MC2R has a significant role in glucocorticoid secretion regulation. The MC2R is selectively activated by the adrenocorticotropic hormone (ACTH), which also causes the adrenal cortex, particularly the zona fasciculata, to produce and secrete glucocorticoids. Recent research has shown that the production of the melanocortin receptor type 2 and its trafficking to the plasma membrane depend on small single-pass transmembrane proteins known as melanocortin receptor auxiliary proteins (MRAP and MRAP2).
Although the MC3R gene is crucial for energy homeostasis, it is less evident than in the case of the MC4R how its polymorphisms or mutations relate to human obesity. This gene was hardly ever examined in domestic mammals.
The melanocortin receptor type 4 is a well-known and important regulator of food intake and energy expenditure. Thus, it has been suggested that the MC4R gene may be a possibility for human obesity.
The MC5R gene is expressed in various peripheral organs, including the skin, as well as the central nervous system. The encoded protein functions in exocrine function, proinflammatory activity, and lipid metabolism, among other physiological activities. In vitro cultured adipocytes with MC5R expression down-regulate leptin secretion and mediate the generation of interleukin 6 (IL6), along with other melanocortin receptor family members. Melanocortin receptor 5 is a functional candidate gene for obesity in humans or fatness in domestic animals due to the correlation between a high level of the IL6 circulating in blood and insulin resistance and the role of leptin in regulating food intake and energy expenditure.
Fig.1 Schematic representation of melanocortin receptor. (Yang, 2011)
Melanocortin Family Drug Discovery
Because of its enormous molecular variety and potential as therapeutic targets, the melanocortin receptor family is one of the most significant classes of GPCR in the genome. The majority of existing ligands operate as the endogenous cognate ligand for the receptor and bind to the orthosteric location to impact melanocortin receptor activity. Allosteric ligands offer a remarkable degree of precision in drug targeting to closely related melanocortin receptor subtypes and induce stimulus-bias in orthosteric ligand signaling, opening up new possibilities for both receptor-selective and signaling-pathway-selective therapies, despite being a still-developing concept in melanocortin receptor pharmacology.
Reference
- Yang, Y. Structure, function and regulation of the melanocortin receptors. European journal of pharmacology. 2011, 660(1): 125-130.
