GPCR contributor article Canonical chemokine receptors as scavenging “decoys” Shivani Sachdev, Brendan

September 2022 "Melanocortin 4 receptor (MC4R) is part of the leptin-melanocortin pathway and plays an essential role in mediating energy homeostasis. Mutations in the MC4R are the most frequent monogenic cause for obesity. Due to increasing numbers of people with excess body weight, the MC4R has become a target of interest in the search of treatment options. We have previously reported that the MC4R forms homodimers, affecting receptor Gs signaling properties. Recent studies introducing setmelanotide, a novel synthetic MC4R agonist, suggest a predominant role of the Gq/11 pathway regarding weight regulation. In this study, we analyzed effects of inhibiting homodimerization on Gq/11 signaling using previously reported MC4R/CB1R chimeras. NanoBRETTM studies to determine protein–protein interaction were conducted, confirming decreased homodimerization capacities of chimeric receptors in HEK293 cells. Gq/11 signaling of chimeric receptors was analyzed using luciferase-based reporter gene (NFAT) assays. Results demonstrate an improvement of alpha-MSH-induced NFAT signaling of chimeras, reaching the level of setmelanotide signaling at wild-type MC4R (MC4R-WT). In summary, our study shows that inhibiting homodimerization has a setmelanotide-like effect on Gq/11 signaling, with chimeric receptors presenting increased potency compared to MC4R-WT. These findings indicate the potential of inhibiting MC4R homodimerization as a therapeutic target to treat obesity." Read more at the source #DrGPCR #GPCR #IndustryNews

So very grateful to the great hard working team we have and all the great achievements we have done together

They found that AF2 models achieved accurate side-chain predictions and successfully docked high-affinity Of 161 molecules tested, 42 substituted more than 50% of [³H]-LSD at 10 μM, achieving a 26% hit rate.

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A number of strategies have been applied to develop CB2 ligands to achieve closer to 'drug-like' properties

A number of strategies have been applied to develop CB2 ligands to achieve closer to 'drug-like' properties

We have achieved a great deal in the last decade, such as the first-ever AI-designed drug candidates

classes, with particular emphasis on those for which protein-based binding assay can be difficult to achieve

PLCβ3, enhances the potency of the antinociceptive effects of morphine suggesting a novel strategy for achieving

monoagonism; therefore, a logical and rational approach is the use of the dual and triagonism of GCPC to achieve

To achieve this, we heterologously expressed human TAS1R2-VFT (hTAS1R2-VFT) in Escherichia coli .

occupy a fraction of the available surface area in the large binding pocket, making them unsuitable for achieving contacts with the receptor at structurally distant sites in the binding pocket, it is difficult to achieve Orion has demonstrated that this target cell-specific delivery cannot be achieved using the native ligand In this model, OB-004 showed powerful efficacy, achieving full blockade of monocyte recruitment in response treatment with mOB-004 dose-dependently suppressed monocyte infiltration into the peritoneum cavity, achieving

Of the 11 with severely reduced cell surface expression, restoration to ≥57% of WT levels was achieved

Chemokines are low molecular weight proteins that their functional activities are achieved by binding

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On the other hand, selectivity could be achieved by merging both orthosteric and allosteric pharmacophores

GPCRs and β-arrestins and how this complex operates on the plasma membrane of living cells was the goal achieved

On the other hand, selectivity could be achieved by merging both orthosteric and allosteric pharmacophores

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Cryo-EM, on the other hand, requires less protein and has evolved to achieve resolutions comparable to