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Until recently, itch pathophysiology was poorly understood and treatments were poorly effective in relieving itch. Current progress in our knowledge of the itch processing, the numerous mediators and receptors involved has led to a large variety of possible therapeutic pathways. Currently, inhibitors of IL-31, IL-4/13, NK1 receptors, opioids and cannabinoids, JAK, PDE4 or TRP are the main compounds involved in clinical trials. However, many new targets, such as Mas-related GPCRs and unexpected new pathways need to be also explored. Read full article

July 2022 Confo Therapeutics receives €1.7 million VLAIO grant for further research on GPCR modulators The grant should help expand Confo Therapeutic’s research on G protein-coupled receptor (GPCR) drug candidates

Drug discovery and development: Role of basic biological research. Biomedical researchers' perspectives on the reproducibility of research. G Protein-Coupled Receptors: A Century of Research and Discovery. The paradox from within: research participants doing-being-observed. Qualitative Research. 2015;16(4):446-467. 56.         Wilner W.

High-content screening (HCS) has become a cornerstone in GPCR and phenotypic drug discovery, enabling researchers The resulting multiparametric datasets are well-suited for GPCR research, where receptor trafficking, For cannabinoid researchers, this capability supports:  Accurate CB2 affinity determination  Visualization For teams working in GPCR pharmacology or cannabinoid research, these tools accelerate hit validation At Celtarys, we remain committed to enabling this transition and supporting researchers as they design

August 2022 A NanoBRET-Based H 3 R Conformational Biosensor to Study Real-Time H 3 Receptor Pharmacology in Cell Membranes and Living Cells "Conformational biosensors to monitor the activation state of G protein-coupled receptors are a useful addition to the molecular pharmacology assay toolbox to characterize ligand efficacy at the level of receptor proteins instead of downstream signaling. We recently reported the initial characterization of a NanoBRET-based conformational histamine H3 receptor (H3R) biosensor that allowed the detection of both (partial) agonism and inverse agonism on living cells in a microplate reader assay format upon stimulation with H3R ligands. In the current study, we have further characterized this H3R biosensor on intact cells by monitoring the effect of consecutive ligand injections in time and evaluating its compatibility with photopharmacological ligands that contain a light-sensitive azobenzene moiety for photo-switching. In addition, we have validated the H3R biosensor in membrane preparations and found that observed potency values better correlated with binding affinity values that were measured in radioligand competition binding assays on membranes. Hence, the H3R conformational biosensor in membranes might be a ready-to-use, high-throughput alternative for radioligand binding assays that in addition can also detect ligand efficacies with comparable values as the intact cell assay." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects. The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation kinetics. Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the presence of PTH or PTHrP at resolutions of 2.8 -4.1 Å. A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP" Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects. The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation kinetics. Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the presence of PTH or PTHrP at resolutions of 2.8 -4.1 Å. A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP." Read more at the source #DrGPCR #GPCR #IndustryNews

Hence, it has wide applicability across a spectrum of neuroscience research, ranging from the study of

Elizabeth Johnstone were awarded one of the 2022 Diabetes Research Grants at the World Diabetes Day Breakfast Perkins Professor Kevin Pfleger and Dr Elizabeth Johnstone who were awarded one of the 2022 Diabetes Research This $60,000 grant from Diabetes Research WA will assist the Perkins' Molecular Endocrinology and Pharmacology

September 2022 "Class A (rhodopsin-like) G protein-coupled receptors (GPCRs) are constitutive phospholipid scramblases as evinced after their reconstitution into liposomes. Yet phospholipid scrambling is not detectable in the resting plasma membrane of mammalian cells that is replete with GPCRs. We considered whether cholesterol, a prominent component of the plasma membrane, limits the ability of GPCRs to scramble lipids. Our previous Markov State Model (MSM) analysis of molecular dynamics simulations of membrane-embedded opsin indicated that phospholipid headgroups traverse a dynamically revealed hydrophilic groove between transmembrane helices (TM) 6 and 7 while their tails remain in the bilayer. Here, we present comparative MSM analyses of 150-μs simulations of opsin in cholesterol-free and cholesterol-rich membranes. Our analyses reveal that cholesterol inhibits phospholipid scrambling by occupying the TM6/7 interface and stabilizing the closed groove conformation while itself undergoing flip-flop. This mechanism may explain the inability of GPCRs to scramble lipids at the plasma membrane." Read more at the source #DrGPCR #GPCR #IndustryNews

Exploring Intracellular Targets: Bridging the Gap Between In Vitro and In Vivo GPCR Research - August and a research associate/scientist in in vitro pharmacology. research within the field of Cellular Biochemistry. Discover the research topic ➤ Why Dr. GPCR scientists, translational pharmacologists, biotech drug discovery teams, and decision-makers who

October 2022 "Single-molecule counting techniques enable a precise determination of the intracellular abundance and stoichiometry of proteins and macromolecular complexes. These details are often challenging to quantitatively assess yet are essential for our understanding of cellular function. Consider G-protein-coupled receptors-an expansive class of transmembrane signaling proteins that participate in many vital physiological functions making them a popular target for drug development. While early evidence for the role of oligomerization in receptor signaling came from ensemble biochemical and biophysical assays, innovations in single-molecule measurements are now driving a paradigm shift in our understanding of its relevance. Here, we review recent developments in single-molecule counting with a focus on photobleaching step counting and the emerging technique of quantitative single-molecule localization microscopy-with a particular emphasis on the potential for these techniques to advance our understanding of the role of oligomerization in G-protein-coupled receptor signaling." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 Luciferase-based GloSensor™ cAMP assay: Temperature optimization and application to cell-based kinetic studies "G protein-coupled receptors (GPCRs) are an important receptor superfamily and common therapeutic targets. The second messenger cyclic adenosine monophosphate (cAMP) is a key mediator in many GPCR signaling pathways. Monitoring intracellular cAMP levels can help identify orthosteric agonists and antagonists, as well as allosteric modulators. In this regard, luminescence-based biosensors have revolutionized our ability to monitor GPCR signaling kinetics. The GloSensor™ cAMP assay enables real-time monitoring of signaling downstream of many GPCRs. However, it is crucial to optimize assay conditions such as temperature. As well, it has not been reported whether the effects of temperature on biosensor activity are reversible. Here, we describe the temperature sensitivity and reversibility of the GloSensor™ cAMP assay, and which GloSensor™ version is optimal for measuring cytosolic cAMP. We also present a detailed protocol for monitoring cAMP levels in live cells expressing endogenous or exogenous GPCRs. Temperature optimization studies were carried out using HEK293H cells transiently transfected with the adenosine receptor A2a and the GloSensor™ plasmid (pGloSensor-20F or -22F). We found that preincubation and luminescence reading at room temperature were optimal as compared to higher temperatures. As well, the GloSensor-22F biosensor had a superior signal-to-background ratio and the effect of temperature on biosensor activity was reversible. However, thermal instability of the biosensor may pose a problem for in vivo studies. Nevertheless, the GloSensor™ cAMP assay can be applied to analyze signaling by a wide range of GPCRs for drug discovery" Read more at the source #DrGPCR #GPCR #IndustryNews

Whether you’re optimizing screening campaigns or navigating translational challenges, these insights moments that changed everything. 👉 Discover the pHSense™ Reagents + Listen to the podcast ➤ Celtarys Research A new contributor article from our friends at Celtrays Research outlines how dual-labeled fluorescent decision-makers. 🚀 Join Premium Today & Enjoy ➤ 🎓 Full GPCR University + 🔬 200+ expert talks 🗞️ Weekly research networking, AMAs & matchmaking 💡 Support open resources for the global GPCR field 🧠 Designed for researchers

GPCR research requires turning data into insights for drug discovery Hi GPCR Friends, Every week, critical decisions in GPCR research hinge on subtle shifts in data. Upcoming events:  Major GPCR-focused symposiums and translational meetings are on the horizon — shaping Career opportunities:  Leadership-level roles in clinical operations and translational science, alongside GPCR scientists, translational pharmacologists, biotech discovery teams, and decision-makers who need

Celtarys Research expands its assay tools with CELT-419 for D3 receptor studies, and Dr. Terry Kenakin brings translational clarity to complex receptor concepts.   The Kenakin Brief Fluorescent Probe CELT-419 Powers D3R Binding Assays Across Platforms   Celtarys Research Maria Majellaro’s path from lab research to co-founding Celtarys, as told in her recent Dr. Explore this week’s research, tools, and biotech insights in one place.

, This week's breakthroughs are crucial for staying ahead in the rapidly evolving landscape of GPCR research Career opportunities:  Explore a selection of high-level job openings in high-throughput screening, research Catherine’s research, blending GPCR signaling studies with public health data, offers critical insights Competitive Edge:  Stay informed on emerging public health threats and the scientific research aimed Shape the next generation of cellular biochemistry research.

Enhance your GPCR research with deeper assay insights for more effective results. Plus: new research on CaSR, leptin signaling, and inflammation-linked GPCRs — and curated roles in computational Design for translation:  Map sensitivity ranges to tissue contexts so your plate data predicts what happens Become a Premium Member today. ➤ 🎓 Full GPCR University + 🔬 200+ expert talks 🗞️ Weekly research, networking, AMAs & matchmaking 💡 Support open resources for the global GPCR field 🧠 Designed for researchers

high-impact insight into GPCR allostery, crafted for pharmacologists and biotech scientists who need to translate Career opportunities:  Exclusive pharma and academic listings you won’t find on job boards—curated for translational Position your research for maximum visibility.   If you work on GPCRs across translational pharmacology, drug development, or molecular pharmacology, GPCR scientists, translational pharmacologists, biotech drug discovery teams, and decision-makers who

Exploring the Hidden Dynamics: How Kinetics Reveals What Equilibrium Conceals in GPCR Research. members get to rewatch the recording Subscribe to the Kenakin Brief and Join the Live AMA ➤ Celtarys Research GPCR scientists, translational pharmacologists, biotech discovery teams, and decision-makers who need master GPCR science — in one membership. 🎓 Full GPCR University + 🔬 200+ expert talks 🗞️ Weekly research networking, AMAs & matchmaking 💡 Support open resources for the global GPCR field 🧠 Designed for researchers

Why CYP450 allostery can make or break translation from bench to bedside. He argues that early-career researchers often fall into the trap of over-rationalizing too soon—missing GPCR scientists, translational pharmacologists, biotech discovery teams, and decision-makers who need Become a Premium Member today. ➤ 🎓 Full GPCR University + 🔬 200+ expert talks 🗞️ Weekly research, networking, AMAs & matchmaking 💡 Support open resources for the global GPCR field 🧠 Designed for researchers

November 22, 2021 JUPITER, FL—Scientists at Scripps Research in Florida have created a collection of

together 80+ senior leaders from biotech and pharma to advance GPCR programmes from discovery through translation — experts in GPCR biology, structural biology, computational design, pharmacology, and translational best practices for measuring GPCR signaling bias in vitro and what that means for in vivo and clinical translation Translational Stories & Clinical Data OMass Therapeutics on long-residence MC2R antagonists.

Fluorescent probes illuminate the mysteries of GPCRs in cutting-edge research. God Molecule"; Novo Nordisk looks to next generation of obesity, diabetes drugs with $550M Replicate research Career opportunities:  Research Assistant; Postdoctoral Associate; Senior Scientist, Data Science—curated roles aligned to GPCR discovery and translational pharmacology. Join Terry's Corner Today ➤ Celtarys Research – Confocal Imaging That Preserves GPCR Function Confocal

equilibrium snapshots, where and when receptors signal, how kinetics shape drug action, and how all of it translates Terry Hébert on iPSC-derived systems for GPCR signaling and translation — recorded April 16.

Since then, the National Human Genome Research Institute (NHGRI) has supported annual events across the country to celebrate, learn and discuss the latest advances in genomic research. This intersection of genomics and GPCR research sparked a new era of a comprehensive understanding of References National Human Genome Research Institute, U. S. (2002) National Human Genome Research Institute.

and kidney fibrosis and pathological angiogenesis, including occurrence of endothelial-to-mesenchymal transition

objective is straightforward: Make mechanistic pharmacology easier to access, revisit, and apply across research functional assays For scientists working in GPCR programs, this connects functional assay data directly to translational

Career opportunities:  Roles spanning research associates to principal scientists across membrane proteins From Bench Frustrations to Breakthrough Design For decades, GPCR trafficking research relied on overexpression chemistry can shift the entire GPCR toolkit. 👉 Go behind the scenes with Revvity’s R&D team ➤ Celtarys Research Because they give researchers something rare in CNS work: clarity in complexity. start here 🚀 Join Premium Today & Enjoy ➤ 🎓 Full GPCR University + 🔬 200+ expert talks 🗞️ Weekly research

However, in epithelial cells, OGR1 promotes epithelial to mesenchymal transition (EMT) and inflammation