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In the realm of molecular research, precise interpretation is crucial; a misread curve can lead to lost GPCR scientists, translational pharmacologists, biotech discovery teams, and decision-makers who need

Celtarys Research Joins Dr. GPCR – Precision Tools for GPCR Assays Dr. GPCR and Celtarys Research have teamed up. Full Breakdown of the Latest in GPCR Research Want detailed insights? Dive into this week’s research, tools, and biotech updates all in one place.

August 2022 "August 10, 2022 Cancer Research UK is working with global biopharma Sosei Heptares on a Cancer Research UK, a charity dedicated to funding lifesaving oncology research, spent £388 million on cancer research last fiscal year. Much of that funding is distributed to support third party research, but the group also does its own research into promising therapy areas, working with partners who have a good idea but don’t have all

to be discussed and to be put in context as soon as possible to be up-to-date and to accelerate the translation

August 2022 "We are proud to announce that SYnAbs is now officially accredited as a Research Tax Credit by the French Ministry of Higher Education and Research for 2022-2023-2024. antibodies #medicine #cancer #innovation #gpcr #synabs #monoclonalantibodies #drugdiscovery #biotechnology #research

December 2021 "Meet Peter McNamara, Ph.D., Tectonic’s SVP, Head of Research.

June 2022 "CRN04894 Selected for Oral Presentation SAN DIEGO, June 8, 2022 — Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), announced that results from the company’s Phase 1 study of CRN04894, the company’s investigational candidate for the treatment of Cushing’s disease, congenital adrenal hyperplasia (CAH) and other conditions driven by excess adrenocorticotropic hormone (ACTH), were selected for an oral presentation at ENDO 2022, the Endocrine Society’s annual meeting. Crinetics recently reported that administration of CRN04894 reduced both serum cortisol levels and 24-hour urine free cortisol excretion in the presence of sustained, disease-like ACTH concentrations in multiple-ascending dose cohorts of a Phase 1 study." Read more at the source #DrGPCR #GPCR #IndustryNews

The newest GPCR research is hot off the press! driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor Methods & Updates in GPCR Research research project - Institute for Protein Design Generate:Biomedicines Fortifies Leadership in Generative Morgan Healthcare Conference Isomorphic Labs Announces Strategic Multi-Target Research Collaboration With Novartis Salipro Biotech announces multi-target research collaboration with an additional Top5 crop

Watch Episode 170 What We’re Missing in Pain Research In GPCR drug discovery, receptors typically steal against chronic pain. ___________ Keyword Cloud: RGS4 , GPCR data platform , GPCR training program , pain research

July 2022 Cancer Research UK and Sosei Heptares sign agreement to advance cancer immunotherapy candidate company and world-leader in GPCR1-focused structure-based drug design (SBDD) and development, and Cancer Research UK, the world’s largest private funder of cancer research, today announce the signing of an agreement

August 2022 Addex and Indivior Extend GABAB Positive Allosteric Modulator Research Collaboration for US $900,000) of additional research funding.

Learning the Lab, Learning Herself During her time at the contract research organization (CRO) in Ann She finally understood what it meant to be driven by a research question, not just assigned to one. For the first time, she saw herself as a future researcher, not just a technician or a student. Technical discipline is transferable—even across research cultures. The Importance of Passion in Research Catherine's journey highlights the importance of passion in research

Watch Episode 172 The Bigger Picture: GPCR Science Meets Public Health At its core, Catherine Demery’s research street-level contamination rising faster than medicine can adapt, Catherine’s work shows why overdose research Catherine’s research confronts this problem head-on by asking: What actually happens to breathing when From Street Samples to Lab Models What makes Catherine’s research particularly powerful is how it stays Without research that keeps pace, clinical tools will always be one step behind.

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 GPCR scientists, translational pharmacologists, biotech drug discovery teams, and decision-makers who

October 2022 β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living cells "β-arrestins mediate regulatory processes for over 800 different G protein-coupled receptors (GPCRs) by adopting specific conformations that result from the geometry of the GPCR-β-arrestin complex. However, whether β-arrestin1 and 2 respond differently for binding to the same GPCR is still unknown. Employing GRK knockout cells and β-arrestins lacking the finger-loop-region, we show that the two isoforms prefer to associate with the active parathyroid hormone 1 receptor (PTH1R) in different complex configurations ("hanging" and "core"). Furthermore, the utilisation of advanced NanoLuc/FlAsH-based biosensors reveals distinct conformational signatures of β-arrestin1 and 2 when bound to active PTH1R (P-R*). Moreover, we assess β-arrestin conformational changes that are induced specifically by proximal and distal C-terminal phosphorylation and in the absence of GPCR kinases (GRKs) (R*). Here, we show differences between conformational changes that are induced by P-R* or R* receptor states and further disclose the impact of site-specific GPCR phosphorylation on arrestin-coupling and function." Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Dr. GPCR Newsletter

January 2022 Exscientia and Sanofi Establish Strategic Research Collaboration to Develop AI-driven Pipeline capabilities and personalised medicine platform from target identification through patient selection Research royalties PARIS & OXFORD, England & BOSTON--Sanofi and Exscientia announced today a groundbreaking research

March 2022 ERNEST has established an Emergency Fund for Ukrainian researchers. "General Eligibility Researchers affiliated to any legal entity in Ukraine (for example, schools and universities, research centers, governmental institutions, or private companies) Deadlines Start of the The purpose of the STSM is to carry out a collaborative research project on topics relevant to the network Our scientific perspective is broad, and we are happy to consider any research proposals from those in

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

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

Our Chief Brainstorm Officer, Attila Foris , is building a system so transparent that anyone joining Learn to translate your program’s internal operational precision into a compelling, de-risked narrative

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

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

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.

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

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

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

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

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