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Orforglipron’s trajectory is redefining weight-management and diabetes markets—implications for GPCR-linked Premium Members get a 50%+ discount when they join Terry’s Corner. 🚨 Live AMA with Dr. Research – Flow Cytometry Reimagined: Fluorescent Ligands vs Antibodies for Live‑Cell GPCR Studies Traditional Fluorescent small-molecule ligands flip the script: direct binding to functional sites, live-cell compatibility Scale confidently:  Use bright, stable ligands for HTS and bias profiling.

Self-docking and cross-docking simulations of G protein-coupled receptor-ligand complexes: Impact of ligand type and receptor activation state G protein-coupled receptors (GPCR) are the largest family of Ligand discovery aimed at identification of chemical tools and drug leads is aided by molecular docking Likewise, the relative importance of receptor activation state and ligand function differences have also after ligand placement.

stabilizes G-protein-coupled receptors (GPCR) in a fully active state and modulates their affinity for bound ligands we investigate the conformational changes induced by the binding of a nanobody (Nb80) on the active-like conformation of the receptor, independent of ligand binding, in contrast to the conditions under which Besides, ligand-specific subtle differences in the conformations assumed by intracellular loop 2 and extracellular loop 2 are captured from the trajectories of various ligand-bound receptors in the presence

October 2022 "The role of different G protein-coupled receptors (GPCRs) in the cardiovascular system is well understood in cardiomyocytes and vascular smooth muscle cells (VSMCs). In the former, stimulation of Gs-coupled receptors leads to increases in contractility, whereas stimulation of Gq-coupled receptors modulates cellular survival and hypertrophic responses. In VSMCs, stimulation of GPCRs also modulates contractile and cell growth phenotypes. Here, we will focus on the relatively less well-studied effects of GPCRs in cardiac fibroblasts, focusing on key signaling events involved in the activation and differentiation of these cells. We also review the hierarchy of signaling events driving the fibrotic response and the communications between fibroblasts and other cells in the heart. We discuss how such events may be distinct depending on where the GPCRs and their associated signaling machinery are localized in these cells with an emphasis on nuclear membrane-localized receptors. Finally, we explore what such connections between the cell surface and nuclear GPCR signaling might mean for cardiac fibrosis." Read more at the source #DrGPCR #GPCR #IndustryNews

We first synthesized a fluorescent ligand enabling equilibrium and kinetic binding studies via NanoBRET Applying this molecular tool in a membrane-based setup and in living cells, we discovered a 4-aminopyrimidine

Specifically controlling the activity of GPCR dimers with ligands is a good approach to clarify their

Humanity has always sought to live longer and for this, multiple strategies have been tried with varying In this sense, G protein-coupled receptors (GPCRs) may be a good option to try to prolong our life while this way, we present the analysis of a series of GPCRs whose activity has been shown to affect the lifespan Our compilation of data revealed that the mechanisms most involved in the role of GPCRs in lifespan are antagonist drugs, depending on the beneficial or harmful effects of each GPCR, in order to prolong people's lifespan

Crystal structures suggest ligand access to the orthosteric binding site of MT1 and MT2 receptors through We investigated the feasibility of this lipophilic entry route for 2-iodomelatonin, a nonselective agonist significantly different in the two receptor subtypes, as assessed by metadynamics simulations, and during ligand melatonin receptor ligands. pocket on the surface of MT1 receptor, which could participate in the recognition of MT1-selective ligands

January 2022 "G-protein-coupled receptors’ star has been on the rise in biotech in recent years as researchers have discovered the vast potential for GPCR-targeting drugs in treating a range of health conditions, from cancer and genetic disorders to inflammation and metabolic imbalances. Among those hitching their wagons to that star are Verily and Sosei Heptares, which have struck a research agreement to discover new GPCR targets that’ll fuel the development of potential drug candidates. The financial details of the strategic collaboration weren’t released, but Sosei Heptares’ past two team-ups in GPCR-based drug discovery have clocked in at $1 billion—with Genentech—and, just last November, $2.6 billion in a partnership with Neurocrine." Read more at the source #DrGPCR #GPCR #IndustryNews

November 2021 "Target class-specific libraries mean you need to screen less to identify high-quality Antibody developers are increasingly utilising antibody libraries to derive high-quality, drug-like biologics As a result, most approved library-derived antibodies originate from just three libraries. To target hard-to-drug targets like G protein-coupled receptors (GPCRs), more libraries, including better and more targeted libraries, are needed."

If the maximal response drops, non-competitive seems like the obvious answer. The real story lies in the rate at which antagonists bind and unbind . Terry also explores the experimental constraints —like timing and equilibrium—that determine whether Terry Kenakin Monthly Ask‑Me‑Anything sessions with live Q&A An expanding on‑demand library for novices The real determinant lies in the kinetics of antagonist binding and unbinding.”

June 2022 "June 15, 2022 06:30 AM EDT - In 2016, Abbie Celniker was promoted to partner at Third Rock Ventures as the firm raised just over $600 million for its fourth fund. Since then, Celniker has helped usher in an additional fund and headed a few startups as interim CEO. Coming on its 15th year, Third Rock Ventures announced its sixth fund today — and largest one by far — at a whopping $1.1 billion. Adding it all up, Third Rock has raised $3.8 billion since its inception. That money has gone to some 60 biotechs, much of it as early funding." Read more at the source #DrGPCR #GPCR #IndustryNews

Neuropathic conditions like neuromas often resist standard opioid treatments. Ben’s approach injects new life into an area most clinicians have given up on. And that’s where the excitement lies: "There’s so much space left to explore in GPCR-targeted modulation

of Gs versus Gi protein coupling selectivity or promiscuity by class A GPCRs and extend the basis of ligand

While traditional drug discovery programs have focused on the development of ligands targeting the binding site of endogenous ligands (orthosteric site), allosteric modulators offer new avenues for the regulation identification of multiple allosteric sites and significantly enhanced our understanding of how allosteric ligands systematic analysis of the currently available GPCR structures in complex with small-molecule allosteric ligands in terms of the location of allosteric pockets, receptor-ligand interactions, and the chemical features

2022 Identification of A2BAR as a potential target in colorectal cancer using novel fluorescent GPCR ligands We selected the adenosine receptor 2B (A2BAR), specifically expressed in cancer cell lines compared with stromal cells, to explore the use of fluorescent ligands that can be used for target visualization. expression of A2BAR in CRC cell lines. As well, fluorescent ligands were effective at monitoring real-time A2BAR receptor labeling using live-imaging

We discuss ligand binding, signaling, and structures of the vGPCRs in light of robust differences from

September 2022 "The complement fragment C5a is one of the most potent proinflammatory glycoproteins liberated C5a is established to interact with a set of genomically related transmembrane receptors, like C5aR1 structure of C5aR2 and its interaction specificity toward C5a is not structurally elucidated in the literature

cell-induced inflammation "Gut intraepithelial lymphocytes (IELs) are thought to calibrate glucagon-like peptide 1 (GLP-1) bioavailability, thereby regulating systemic glucose and lipid metabolism. -1RAs require the gut IEL GLP-1R to selectively restrain local and systemic T cell-induced, but not lipopolysaccharide-induced Such effects are mediated by the suppression of gut IEL effector functions linked to the dampening of These data reposition key roles of the L cell-gut IEL GLP-1R axis, revealing mechanisms linking GLP-1R

In particular, focus lies on the mechanism behind the techniques, and the specific advantages and challenges that one should consider when attempting to compare functional outcomes from different studies, both linked to the specific assay mechanism and linked to its specific execution, as these may heavily impact the

pro-inflammatory settings and clinical trials to treat idiopathic pulmonary fibrosis are currently ongoing using ligands

I would like to take this opportunity to thank all our French partners who trust us in the generation #technology #lifescience #immunology #antibodies #medicine #cancer #innovation #gpcr #synabs #monoclonalantibodies

#biotech #lifesciences #appointment #GPCR #Oncology" Read more at the source #DrGPCR #GPCR #IndustryNews

Breakthroughs this week: Decoding ADGRE5 signaling; Eli Lilly’s obesity pill vs Novo’s Wegovy; Certa Metabolic GPCRs in the spotlight; receptor motion tracking tools; obesity treatment race between Eli Lilly From biased ligands to computational targeting, this is where the pipelines of the 2030s begin. DrGPCR University Attendee The difference between stalled programs and breakthrough therapies often lies

understanding why two drugs with similar affinity may behave completely differently , and how the secret lies Ligands don’t just “bind”—they change  the receptor. These sites don’t behave like traditional active sites. Ligands may take hours to equilibrate , even when they look potent on paper. What If the Same Site Behaves Differently Depending on the Ligand?

These probes shift brightness and fluorescence lifetime as pH changes. Revvity commercial launch Building a Scalable Platform — Not a One-Off Assay The brilliance of pHSense lies “It’s like a funnel,” Trinquet explains. To hear the full story of how pHSense came to life—and why the GLP-1 data changed everything— 🎧 Listen GPCR X Revvity Collaboration ⸻ Want more like this? 👉 Join the Dr.

Liu S, Anderson PJ, Rajagopal S, Lefkowitz RJ, Rockman HA. Wodak SJ, Paci E, Dokholyan NV, Berezovsky IN, Horovitz A, Li J, et al. Motlagh HN, Wrabl JO, Li J, Hilser VJ. The ensemble nature of allostery. Shen S, Zhao C, Wu C, Sun S, Li Z, Yan W, et al. Truong ME, Bilekova S, Choksi SP, Li W, Bugaj LJ, Xu K, et al.

Receptors in Hepatic Stellate Cells and Approaches to Anti-Fibrotic Treatment of Non-Alcoholic Fatty Liver Disease The prevalence of non-alcoholic fatty liver disease (NAFLD) is globally increasing. Like many other organs, various GPCRs play a role in regulating liver function. It is predicted that more than 50 GPCRs are expressed in the liver. of the liver is very limited.

In particular, we focus on the application of on-cell NMR spectroscopy to characterize ligand interactions techniques allow for quantification of binding affinities, competitive binding assays, delineation of ligands involved in binding, ligand bound-state conformational determination, evaluation of receptor structuring and dynamics, and inference of distance constraints characteristic of the ligand-receptor bound state

Toll-like receptor 4 (TLR4) is one such non-GPCR receptor, which involves MyD88-dependent and TRIF-dependent