Search Results

In the current report we present evidence of the modulation of PK2/PKR2 activity by anosmin 1, since cysteine-rich (CR) and the FnIII.1 domains could assist the WAP domain both in the binding to PKR2 and in the modulation

Extracts from plants, fungi, bacteria, and environmental microorganisms provided the first potent modulators Kenakin highlights how hybrid molecules  — combining two pharmacophores into one scaffold — enable dual-modality This enables: Positive Allosteric Modulators (PAMs) — enhance natural signaling Negative Allosteric Modulators Functionally selective ligands Better therapeutic windows More predictable clinical behavior Allosteric modulation They offer high specificity , favorable safety , and unique mechanisms , including GPCR modulation through

We demonstrate how tail composition plays a role in modulating the binding of PI(4,5)P2 lipids to GCGR

proteins in regulating basal, dopamine-induced and cAMP/PKA-dependent transcription in rat striatal neurons The activity of striatal medium-spiny projection neurons is regulated by D1 and D2 dopamine receptors whether BET proteins, or Brd4 specifically, are involved in transcriptional activation by cAMP/PKA in neurons JQ1 treatment downregulated expression of many GPCRs and also impaired ERK1/2 signalling in striatal neurons , and delineate complex bi-directional effects of bromodomain inhibitors on neuronal transcription.

September 2022 β2-Adrenergic Receptor Expression and Intracellular Signaling in B Cells Are Highly Dynamic during Collagen-Induced Arthritis "The sympathetic nervous system (SNS) has either a pro-inflammatory or anti-inflammatory effect, depending on the stage of arthritis. In the past, treatment of arthritic B cells with a β2-adrenergic receptor (β2-ADR) agonist has been shown to attenuate arthritis. In this study, the expression and signaling of β2-ADR in B cells during collagen-induced arthritis (CIA) were investigated to provide an explanation of why only B cells from arthritic mice are able to improve CIA. Splenic B cells were isolated via magnetic-activated cell sorting (MACS). Adrenergic receptors on B cells and intracellular β2-ADR downstream molecules (G protein-coupled receptor kinase 2 (GRK-2), β-Arrestin 2, p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB)) were analyzed at different time points in naïve and arthritic B cells with and without stimulation of β2-ADR agonist terbutaline by flow cytometry. β2-ADR-expressing B cells increase during CIA without a change in receptor density. Moreover, we observed a profound downregulation of GRK-2 shortly after induction of arthritis and an increase in β-Arrestin 2 only at late stage of arthritis. The second messengers studied (p38, ERK1/2 and CREB) followed a biphasic course, characterized by a reduction at onset and an increase in established arthritis. Stimulation of CIA B cells with the β-ADR agonist terbutaline increased pp38 MAPK independent of the timepoint, while pERK1/2 and pCREB were enhanced only in the late phase of arthritis. The phosphorylation of p38 MAPK, ERK1/2 and CREB in the late phase of arthritis was associated with increased IL-10 produced by B10 cells. The change of β2-ADR expression and signaling during sustained inflammation might be an integral part of the switch from pro- to anti-inflammatory action of sympathetic mechanisms in late arthritis." Read more at the source #DrGPCR #GPCR #IndustryNews

Join us for the first virtual cafe talk to hear about the amazing work that Dr. Brian Arey is doing. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

their transducer coupling, biased angiotensin receptor ligands, and circuit-selective analgesia in pain models Separate effect size from time:  Use allosteric modulators to expand therapeutic index and reduce overdose

Most GPCR programs don’t fail because of weak molecules—they fail because biology behaves differently than the assay implied. This week’s feature goes straight to the foundation: how system-level GPCR thinking  protects discovery teams from the costly misinterpretations that derail programs. If your work touches GPCR pharmacology, these insights aren’t optional—they’re essential. Breakthroughs this week: Eli Lilly cuts Zepbound prices; GNAI1 missense mutation study; rapid Gαs endosomal translocation. 🔍 This Week in Premium: Sneak Peek Industry insights:  Lilly cuts Zepbound prices; Lilly hits $1T valuation; Novo advances amycretin. Upcoming events:  Adhesion GPCR Workshop; GRC—Transporters, Ion Channels & GPCRs; MPGPCR Joint Satellite Meeting. Career opportunities:  Senior/Principal Scientist—GPCR Pharmacology; Principal Scientist—In Vitro Pharmacology; Research Associate—Biologics Discovery. Must-read publications:  Gαi1 neurodevelopmental mutation; Gαs endosomal signaling; primary cilia as transduction hubs. Terry’s Corner: GPCR Pharmacology Insights That Prevent Real Drug Discovery Failures Discovery collapses when teams assume stable, linear, receptor-to-response relationships. Dr. Kenakin’s AMA made the central point unmistakable: GPCR systems constantly reshape ligand behavior through coupling efficiency, receptor density, local signaling architecture, and physiological feedback loops. This is where system-level GPCR thinking  becomes a competitive advantage—long before a molecule reaches animals or patients. When you see the distortions baked into the system, you interpret your data differently and protect your program from preventable failures. What You’ll Gain Spot false confidence early  → Sensitivity differences can turn full agonists into partials or even antagonists depending on system load. Avoid misleading mechanistic labels  → NAMs, PAMs, and biased agonists behave in system-dependent ways that single assays cannot reveal. Translate potency and efficacy realistically  → Recognize when deviations reflect biology rather than compound failure. Premium Members get 67% discount when they join Terry’s Corner in 2025 Sharpen your interpretation skills ➤ Dr. GPCR Podcast: Chemical Probes for GPCR Imaging with Dr. Johannes Broichhagen Reliable imaging tools change how researchers see receptor behavior. In this episode, Dr. Johannes Broichhagen explains how next-generation fluorescent probes—designed with precise synthetic logic—enable deeper insight into GPCR internalization, trafficking, and surface organization. His work shows why chemical design can outperform antibodies and how rigorous assay validation bridges chemistry and biology effectively. What You’ll Learn Why peptide–fluorophore probes succeed where antibodies fail How parallel synthesis& testing accelerates probe optimization How surface-exposed receptor pools reshape interpretations of trafficking Listen to the episode ➤ High-Content Screening for GPCR Programs: Overcoming Assay Limitations with Fluorescent Ligands High-content screening (HCS) is now indispensable for GPCR workflows—especially when spatial context, trafficking behavior, and live-cell kinetics matter. But HCS only works when assays are built with rigor and powered by the right fluorescent ligands. This feature from Celtarys Research outlines how to structure an HCS workflow that avoids batch effects, imaging artifacts, and variability while delivering reliable, mechanistic data. What You’ll Learn Why traditional radioligand assays miss critical spatial and kinetic signals Five phases of a robust, reproducible HCS pipeline How fluorescent ligands strengthen specificity, relevance, and assay confidence Read the full HCS feature ➤ Why System-Level GPCR Thinking Changes Data Interpretation And How Dr. GPCR Premium Membership Gives You an Edge Premium gives GPCR scientists and biotech teams a single, trusted source of weekly insight that cuts through noise. Members access deep-dive lectures, expert frameworks, curated jobs, upcoming events, and classified more. It’s a system-aware resource built for researchers who need clarity fast—reinforcing system-level GPCR thinking  every week so your interpretations stay sharp and aligned with real biology. FAQ 🔹 What’s included? Weekly research, careers, and industry intelligence; GPCR University; 200+ expert talks; networking; and member-only discounts. 🔹 Who is it for? Researchers, pharmacologists, biotech teams, and decision-makers who rely on accurate, efficient, interpretation-first information. 🔹 Why now? GPCR innovation is accelerating—and misinterpretation compounds quickly. Staying informed today prevents the delays others won’t see coming. Don’t Fall Behind—Access the Edge You Need Already a Premium Member? 👉 Access this week’s full Premium Edition here ➤ What Members Say "I am a convert! I will keep Dr. GPCR and the offered resources in my work sphere." Help us reach more scientists by providing quick rating on Spotify or Apple Podcasts — and a YouTube subscribe. Spotify: https://open.spotify.com/show/1KQHbC2qhkRIrdgBDtiQVF Apple Podcasts: https://podcasts.apple.com/us/podcast/dr-gpcr-podcast/id1514231064 YouTube: https://www.youtube.com/@DrGPCR Want to support Dr. GPCR? Donate : https://www.ecosystem.drgpcr.com/donate Dr. GPCR is a 501(c)(3) non-profit organization—your participation directly supports our mission to advance GPCR research and education across the global community.

Slopes <1  may reveal allosteric modulation , where the antagonist binds at a secondary site. The model’s flexibility accommodates both agonism and antagonism as long as the analysis targets equilibrium Modern pharmacology has powerful modeling software, yet Schild analysis remains the litmus test for mechanism

2022 Structural perspectives on the mechanism of signal activation, ligand selectivity and allosteric modulation

However, the channel is expressed in various tissues and cell types including neurons as well as glial developments with particular focus on findings from studies involving ocular tissues and cells or peripheral neurons

Venetia Zachariou  introduced him to the power of RGS proteins — particularly RGS4  — in modulating pain recovery that is very rare to see at the preclinical level. " Such recovery is rare in preclinical pain models and hints that RGS proteins could modulate pain chronification itself .

GPCR Binders, Drugs, and more Allosteric modulation of a human odorant receptor. Single-cell transcriptome analysis of NEUROG3+ cells during pancreatic endocrine differentiation with assays allow the analysis of binding kinetics of WNT-3A to endogenous Frizzled 7 in a colorectal cancer model

in isolation—they respond to the system they’re in, often through opposing processes that you must model In this session, you’ll gain: ✅ A mental model you can trust  for predicting how GPCR ligands behave This section outlines the logic required to match preclinical models to patient physiology and avoid In this module, you’ll explore how some receptor–agonist complexes continue signaling from endosomes, Your molecule isn’t failing—your model might be too simple.

Welcome back GPCR fans, If your drug discovery strategy still relies on static GPCR models, you’re already Leverage this model to stay ahead of therapeutic complexity. It’s the 20th anniversary—and the spotlight is squarely on kinetic modeling, allosteric frameworks, and Access peer insights on allosteric modulators and biased ligands.

Before the advent of AlphaFold, homology modeling was the most common method for predicting G protein-coupled Homology modeling relies on using the known structure of a homologous protein as a template to model For proteins with low sequence similarity to available templates, homology models tend to be less accurate targeting TAAR1, more than double that of the homology models. Ligand discovery from a dopamine D3 receptor homology model and crystal structure.

Additionally, GPCR dysregulation underlies multiple models of cardiac pathology, and most pharmacological Current literature strongly establishes increased levels and activity of GRK2 in multiple models of CVD the GRK2 interactome includes numerous proteins which interact with differential domains of GRK2 to modulate the ongoing and future research for targeting this critical kinase across cellular, animal and human models

GPCR Symposium on 'GPCRs as Therapeutic Modalities' is set for September 22nd. treatment of cardiometabolic disease GPCRs in Neuroscience Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson's disease mouse model through activating GHS-R1a/D2R heterodimers GPR37L1 controls diseases Ultrasensitive dose-response for asbestos cancer risk implied by new inflammation-mutation model the GPCR Smoothened and to the germline inducer Oskar Industry News Addex GABAb Positive Allosteric Modulator

They include small molecules that conditionally modulate proteins in their functional state; three-dimensional (3D) cell models, or organoid models, that assist with target identification, high-throughput drug screening

Dopamine D2 receptor modulators  – transforming treatment for Parkinson’s & schizophrenia. Allosteric modulation  for unprecedented precision. Serotonin & dopamine receptor modulation  for neuropsychiatric disorders. These sessions bridge structural biology , computational modeling , and clinical translation  — with

in Drosophila Neurons Dr. sensing of mechano- and ligand-dependent adhesion GPCR dissociation GPCR Activation and Signaling GPR101: Modeling and more Discovery of Guanfacine as a Novel TAAR1 Agonist: A Combination Strategy through Molecular Modeling Methods & Updates in GPCR Research GproteinDb in 2024: new G protein-GPCR couplings, AlphaFold2-multimer models and interface interactions Experimental modulation of physiological force application on leg joint neurons

By modulating receptor expression or sensitivity, we can shift the “lens” through which drug activity Model patient-like pathophysiological states (e.g., reduced receptor expression in heart failure). Adjusting assay sensitivity—whether through expression systems, chemical modulation, or engineered desensitization—provides landscape is dynamic—ligands compete, cooperate, and reshape receptor ensembles in ways that standard models

research on the Relevance of GPCR dynamics for receptor activation, signalling bias and allosteric modulation promoting G protein translocation to endosomes GPCRs in Neuroscience An atlas of GPCRs in dopamine neurons G protein-coupled receptor (GPCR) dynamics for receptor activation, signalling bias and allosteric modulation Comprehensive Conformational Rearrangements of a G Protein-Coupled Receptor Influence of the Water Model Interactions of the GPR40 Protein with the Lipid Membrane and the Solvent: Rigid versus Flexible Water Models

Adhesion GPCRs A screen of pharmacologically active compounds to identify modulators of the Adgrg6/Gpr126 Modulation of GPCR receptors common to gut inflammatory diseases and neuronal disorders, Alzheimer's Internal and external modulation factors of the orexin system (REVIEW). Structure-based pharmacophore modeling 2. Developing a novel framework for structure-based pharmacophore model generation and selection.

Our previous work demonstrated that GPR3-mediated β-arrestin signaling modulates amyloid-β (Aβ) generation Here, we generated a G protein-biased GPR3 mouse model to investigate the physiological and pathophysiological leads to a decrease in the area and compaction of amyloid plaques in the preclinical AppNL-G-F AD mouse model

August 2022 "GPCRs modulate a plethora of physiological processes and mediate the effects of one-third implementation of the guidelines, together improving translation from in vitro to disease-relevant in vivo models

Alexander S Hauser GPCRdb in 2025: adding odorant receptors, data mapper, structure similarity search and models anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M1 Receptor The cell adhesion molecule CD44 acts as a modulator of 5 pharmacogenomics research GPCRdb in 2025: adding odorant receptors, data mapper, structure similarity search and models

Subacute SCI is mainly characterized by neuronal apoptosis, axonal demyelination, Wallerian degeneration The models of the three gene expression profiles were all for SCI to the thoracic segment of the rat. Module analysis was performed using Cytoscape.

Lyu et al. prospectively docked ultra-large libraries of molecules against unrefined AF2 models of the They found that AF2 models achieved accurate side-chain predictions and successfully docked high-affinity Docking 490 million molecules against the σ2 receptor's AF2 model yielded a 54% hit rate, comparable Moreover, advanced AI models like AlphaFold3, which can predict complex protein-molecule interactions This proprietary nature limits direct access to the model and imposes a cap on daily predictions.

ML algorithms typically use traditional ML models, such as decision trees and support vector machines While classical ML models are effective for datasets for which the relevant features are well understood which comprise handcrafted features and simpler models. For this reason, DL models generally require more computational resources (such as powerful GPUs) and Classification: AI models can be used to distinguish GPCRs from non-GPCRs, and to classify GPCRs into