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October 2022 Cholesterol-Dependent Dynamics of the Serotonin1A Receptor Utilizing Single Particle Tracking: Analysis of Diffusion Modes "G protein-coupled receptors (GPCRs) are signaling hubs in cell membranes that regulate a wide range of physiological processes and are popular drug targets. Serotonin1A receptors are important members of the GPCR family and are implicated in neuropsychiatric disorders. Cholesterol is a key constituent of higher eukaryotic membranes and is believed to contribute to the segregated distribution of membrane constituents into domains. To explore the role of cholesterol in lateral dynamics of GPCRs, we utilized single particle tracking (SPT) to monitor diffusion of serotonin1A receptors under acute and chronic cholesterol-depleted conditions. Our results show that the short-term diffusion coefficient of the receptor decreases upon cholesterol depletion, irrespective of the method of cholesterol depletion. Analysis of SPT trajectories revealed that relative populations of receptors undergoing various modes of diffusion change upon cholesterol depletion. Notably, in cholesterol-depleted cells, we observed an increase in the confined population of the receptor accompanied by a reduction in diffusion coefficient for chronic cholesterol depletion. These results are supported by our recent work and present observations that show polymerization of G-actin in response to chronic cholesterol depletion. Taken together, our results bring out the interdependence of cholesterol and actin cytoskeleton in regulating diffusion of GPCRs in membranes." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Bell-Evans model and steered molecular dynamics in uncovering the dissociation kinetics of ligands targeting G-protein-coupled receptors "Recently, academic and industrial scientific communities involved in kinetics-based drug development have become immensely interested in predicting the drug target residence time. Screening drug candidates in terms of their computationally predicted residence times, which is a measure of drug efficacy in vivo, and simultaneously assessing computational binding affinities are becoming inevitable. Non-equilibrium molecular simulation approaches are proven to be useful in this purpose. Here, we have implemented an optimized approach of combining the data derived from steered molecular dynamics simulations and the Bell-Evans model to predict the absolute residence times of the antagonist ZMA241385 and agonist NECA that target the A2A adenosine receptor of the G-protein-coupled receptor (GPCR) protein family. We have predicted the absolute ligand residence times on the timescale of seconds. However, our predictions were many folds shorter than those determined experimentally. Additionally, we calculated the thermodynamics of ligand binding in terms of ligand binding energies and the per-residue contribution of the receptor. Subsequently, binding pocket hotspot residues that would be important for further computational mutagenesis studies were identified. In the experiment, similar sets of residues were found to be in significant contact with both ligands under study. Our results build a strong foundation for further improvement of our approach by rationalizing the kinetics of ligand unbinding with the thermodynamics of ligand binding." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 Production of human A 2A AR in lipid nanodiscs for 19 F-NMR and single-molecule fluorescence spectroscopy "We describe production of the human A2A adenosine receptor (A2AAR), a class A G protein-coupled receptor (GPCR) for 19F-NMR and single-molecule fluorescence (SMF) spectroscopy. We explain in detail steps shared between the two sample preparation strategies, including expression and isolation of A2AAR and assembly of A2AAR in lipid nanodiscs and procedures for incorporation of either 19F-NMR or fluorescence probes. Protocols for SMF experiments include sample setup, data acquisition, data processing, and error analysis. For complete details on the use and execution of this protocol, please refer to Wei et al. (2022) and Sušac et al. (2018)." Read more at the source #DrGPCR #GPCR #IndustryNews

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

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

Yet that summer research placement cracked open a new reality: the thrill of asking questions no one She went from reluctant intern to global researcher shaping how we understand GPCR spatial signaling. This pivot reflects a universal research truth: origin stories evolve—but the spark remains . For her, leadership in GPCR research is about enabling others to find their spark the way she found hers For GPCR research, leaders like Michelle are showing what happens when we follow the signal all the way

of attention because of its involvement in various diseases, such as idiopathic pulmonary fibrosis, cancers

That perspective changed the moment he entered GPCR research . Instead, he acts as an advisor, helping research teams decide where modeling can accelerate progress—and The GPCR Challenge What makes collaboration non-negotiable in GPCR research is the biology itself. Whether in academia or biotech, the future belongs to research groups that can orchestrate ecosystems GPCR Models Don’t Discover Drugs—People Do In GPCR research, the biggest breakthroughs won’t come from

Career opportunities:  A curated list of new positions, including a Research Associate, a Senior Research Scientist, and a Post-doctoral Researcher position focused on GPCRs and Mitochondria. We’ve also highlighted the latest research on non-canonical internalization mechanisms of mGlu receptors the actionable intelligence you need to make sense of these trends and integrate them into your own research

sensory #ionchannels to the group leader at the University of Utah investigating Class F #GPCRs in #cancer

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

, arrestins, and effectors, activate downstream pathways that often modulate hallmark mechanisms of cancer To test this possibility, we systematically aggregated somatic cancer mutations across class A GPCRs Individual cancer types were enriched for highly impactful, recurrent mutations at selected cognate positions The possibility that multiple different GPCRs could moonlight as drivers or enablers of a given cancer through mutations located at cognate positions across GPCR paralogs opens a window into cancer mechanisms

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

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

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

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.

Tackling the GPCR Imprecision Problem: Strategic Planning for Sustainable Progress in Complex Systems. In the high-stakes world of GPCR drug discovery , breakthrough science isn't enough. You can have the most brilliant minds and cutting-edge assays, but if your science isn't continuously integrated with your GPCR operational strategy and investment goals, even the most promising program can falter. This fundamental disconnect between the lab and the boardroom  is precisely where programs get stuck—not because of bad science, but because companies find themselves throwing more money and people at problems that could be solved with better systems. This reactive approach, driven by a "go fast" mindset, burns through precious capital and time, leaving both scientific teams and investors frustrated. Companies find themselves throwing more money and people at problems that could be solved with better systems . This reactive approach, driven by the prevailing wisdom of "going fast" and focusing only on the science, burns through precious capital and time, leaving both scientific teams and investors frustrated. This belief that we don't have time to build better systems is a costly miscalculation. It reminds me of a conversation I recently overheard: my oldest child complaining about having to do 'everything at the same time ,' only for the youngest to wisely respond, 'No, you just need to do one thing at a time .' This simple truth applies profoundly to the "go fast" culture in biotech. We believe we don't have time to build better systems, but in reality, our most brilliant and expensive minds are stuck with low-impact tasks due to a lack of systems thinking . My perspective on this challenge is shaped not by a 40-year journey at the bench, but by an expertise in systems thinking  and operational discipline . My work isn't just  about the latest and best assay; it's about the framework that ensures the right assay data leads to the right decision. This is the critical piece that often gets lost in the "go fast" culture—the integration of science with strategy and flawless execution. I’ve lived this firsthand, not just in theory, but by building these systems from the ground up. I understand that embracing a systematic approach can feel daunting, especially with the pressure to move quickly. At Dr. GPCR, we recognized this core problem. Our Chief Brainstorm Officer, Attila Foris , is building a system so transparent that anyone joining the company can integrate seamlessly. Every time a problem arises, we trace it back to its root cause, implementing changes that prevent its recurrence. This iterative process of continuous, planned improvement ensures you're always addressing the next critical area. This is the essence of de-risking GPCR programs through operational excellence. This kind of continuous improvement doesn't happen organically; it demands intentional planning and a systematic approach, ensuring every step forward is strategic and sustainable. The Role of Systems Thinking in GPCR Drug Discovery Systems thinking is the intentional practice of seeing the entire GPCR program as a single, interconnected entity. It's the opposite of a reactive approach, where problems are solved in isolation. It’s the fundamental framework for building your Precision Blueprint , ensuring every scientific detail, operational process, and strategic decision aligns to create a seamless, predictable pathway to success. What You'll Learn in This Series Over the next five bi-weekly installments, " The GPCR Precision Blueprint " series will unpack how to bridge this critical gap. I'll show you how to transform your drug discovery process from a series of disconnected efforts into a seamless, predictable, and de-risked pathway. Part 1: The GPCR Imprecision Problem : I'll reveal why reliance on hiring more people over investing in robust systems thinking  is a multi-million dollar mistake. We'll look at how overlooked operational details, such as misaligned data from diverse GPCR assay types or communication gaps in cross-functional collaboration , lead to critical costs. Part 2: The Data Disconnect : Discover how fragmented, unmanaged GPCR data  cripples scientific progress and strategic decision-making. Learn how to build an integrated data pipeline  that transforms this chaos into a strategic asset. Part 3: The Financial Friction : Explore how a lack of precise alignment between GPCR scientific milestones  and financial realities creates significant risk. Learn to tie your program's progress directly to your funding runway, incorporating crucial early commercial and medical foresight. Part 4: The Investor Imperative : Understand what investors truly prioritize beyond just great science. Learn to translate your program’s internal operational precision into a compelling, de-risked narrative  that builds confidence and secures critical venture capital . Part 5: Your Precision Blueprint : I'll tie it all together, providing a concise, actionable guide for implementing this holistic approach within your own GPCR operational strategy , emphasizing that precision is a continuous, intentional journey towards predictable success. The GPCR Precision Blueprint is more than a concept. If you're ready to move beyond the articles and build these systems for your own GPCR program, let's connect. I work with biotechs, VCs, and CROs to implement the framework that ensures every step forward is strategic and sustainable, offering precision scientific and operational guidance  to accelerate discovery . 🚀 Book your free 30-minute strategy call Let’s unlock the momentum your GPCR program needs. 👉 https://calendly.com/drgpcr/yamina-corner Or explore how we can work together: 👉 Yamina.org

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

Exploring Intracellular Targets: Bridging the Gap Between In Vitro and In Vivo GPCR Research - August and a research associate/scientist in in vitro pharmacology. GPCR Podcast : The Future of GPCR Drug Discovery with Molecular Modeling The field of GPCR research is research within the field of Cellular Biochemistry. Discover the research topic ➤ Why Dr.

Miles Thompson, Alexander Hauser, Caroline Gorvin et al. for their research on GPCR gene variants and April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK colitis GPCRs in Oncology and Immunology Polarizing itch Biochemical pharmacology of adenylyl cyclases in cancer protein-coupled receptor (GPCR) gene variants and human genetic disease Advances and challenges in cancer Inflammatory Bowel Disease (IBD) Domain Therapeutics and Chime Biologics Form Manufacturing Pact for Antibody Cancer

Embark on this week’s thrilling updates in GPCR research, learning opportunities, and industry developments Innovate UK announced the winners of its Transforming Cancer Therapeutics grant, which focuses on developing life-changing cancer treatments. Europe July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs HIGHLIGHT Research power of many: Multilevel targeting of representative chemokine and metabolite GPCRs in personalized cancer

Celtarys Research expands its assay tools with CELT-419 for D3 receptor studies, and Dr. Phosphorylation’s selective role in β-arrestin recruitment across class B1 GPCRs  – GPCR mutations in cancer—drivers Maria Majellaro’s path from lab research to co-founding Celtarys, as told in her recent Dr. GPCR mutations in cancer   show both driver-like patterns and high redundancy, prompting a call for multiomics Explore this week’s research, tools, and biotech insights in one place.

This Thursday, explore the latest content on GPCRs, which includes 29 informative research papers and Stay informed about the most recent developments in GPCR research and industry updates. Metallo-protease Peptidase M84 from Bacillusaltitudinis induces ROS-dependent apoptosis in ovarian cancer receptor-related gene signature through bioinformatics analysis to construct a risk model for ovarian cancer and Discovery Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer

This week's highlight includes congrats to: Junyi Liang, Niña Caculitan, and Adam W Smith for their research on β2-adrenergic receptor associates with CXCR4 multimers in human cancer cells Dr. April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK GPCRs in Oncology and Immunology The β2-adrenergic receptor associates with CXCR4 multimers in human cancer Therapeutics Announces Publication in PNAS Using Cutting Edge Spectroscopy to Detect GPCR Heteromers on Live Cancer

We have gathered 24 new research papers on GPCRs and updates on industry news related to GPCRs. Kawthar Belkacemi, Philippe Rondard, Jean-Philippe Pin, and Laurent Prézeau, for their research on Heterodimers in Oncology and Immunology Metabolic crosstalk: Extracellular ATP and the tumor microenvironment in cancer progression and therapy Agonists of galanin subtype 2 receptor may prevent pancreatic cancer and agonists of angiotensin II type 2 receptor may prevent colorectal cancer Distinct Activation Mechanisms of CXCR4

Small-molecule targeting of GPCR-independent noncanonical G-protein signaling in cancer. Methods & Updates in GPCR Research NanoBiT- and NanoBiT/BRET-based assays allow the analysis of binding kinetics of WNT-3A to endogenous Frizzled 7 in a colorectal cancer model. RGS proteins and their roles in cancer: friend or foe?. yeast-based dual biosensor for detecting peptide variants The Galien Foundation Announces 2023 Prix Galien UK

adhesion G protein-coupled receptors as potential therapeutic targets in Uterine Corpus Endometrial cancer the G protein-coupled receptors (GPCRs) superfamily, have gradually entered the field of vision of researchers The structure, function, and involvement of adhesion GPCRs in cancer development have been discussed epithelial, whichis alsooneofthemostcommonfemalereproductivesystemtumors, but there are few pieces of research

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

to: Makaía M Papasergi-Scott, Peter Gmeiner, Brian K Kobilka, Georgios Skiniotis, et al. for their research Interested in showcasing your research? April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK Therapeutics and Chime Biologics announce manufacturing agreement  to advance novel anti-CCR8 antibody  for cancer , optical imaging, substance use disorder, pharmacology Research Fellow Postdoctoral Fellow – Molecular