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Must-read publications:  β-arrestin2-biased allosteric modulator for pain beyond opioids & GPR3 regulated Physiological relevance:  Fluorescent ligands can retain receptor integrity—critical when signaling readouts

Watch Episode 167 What started with a single receptor became a toolset for an entire superfamily. Tom Sakmar didn’t set out to map GPCR-RAMP interactions across hundreds of receptors. began with a phone call (from Bruce Merrifield, no less) encouraging Sakmar to work on the glucagon receptor A Long-Term Obsession, Reframed Sakmar’s lab had been focused on the secretin receptor family  for decades It was graduate student Emily Lorenzen  who helped frame the next step: stop studying one receptor at

Understanding receptor-ligand interaction is key in drug discovery and biomedical research. Besides binding assays, they can also be used to study receptor density, binding sites and ligand kinetics interactions, particularly in pharmacokinetic and receptor occupancy studies. They are useful tools to visualize receptors in native or transfected cells, whether living or fixed. Probing the pharmacology of G protein-coupled receptors with fluorescent ligands.

Azietaku , our great contributor, for his article Class B1 GPCR Dimerization: Unveiling Its Role in Receptor variant in RGS18 candidate for a familial mild bleeding syndrome Fusarium graminearum Ste2 and Ste3 Receptors Heterodimerization when Expressed Heterologously in Saccharomyces cerevisiae The beta 2 adrenergic receptor Neuronal Precursor Cells Derived from Patients Diagnosed with Schizophrenia Sphingosine 1-phosphate receptor the CaSR gene Reviews, GPCRs, and more Insight into structural properties of viral G protein-coupled receptors

Pharmacology isn’t only about ligands, receptors, and downstream G protein signaling—it’s also about In this course, you’ll gain: ✅ How assay volume control  alters receptor sensitivity and what that By modulating receptor expression or sensitivity, we can shift the “lens” through which drug activity Why System Sensitivity Matters Consider the signaling cascade: ligand binds receptor, receptor couples Think of it this way: most receptors behave like switches—they stay off until flipped.

We’re also spotlighting breakthroughs that challenge dogma and deepen our view of receptor dynamics, from the surprising discovery that β-arrestin can bind GPCRs without receptor activation, to visualizing A new cell-based tool detects receptor activity and reveals endogenous ligands.   A powerful three-color approach captures dynamic receptor states in real time. Whether you're decoding a hidden receptor state or hunting for the next orphan GPCR ligand, we're here

Kotliar , Thomas Sakmar , et al. for their study on Multiplexed mapping of the interactome of GPCRs with receptor activity-modifying proteins Molecular mechanism of bitter taste receptor agonist-mediated relaxation Urotensin II Peptide Analogues: A Proposed Key Role of the N-Terminal Region for Novel Urotensin II Receptor Modulators GPCRs in Oncology and Immunology G protein-coupled receptor-mediated signaling of immunomodulation variants and human genetic disease Advances in yeast synthetic biology for human G protein-coupled receptor

This makes them very useful for GPCR drug discovery, since receptors are a lot bigger than their small where they used CELT-419 for D3 dopamine receptor binding assays in baculoviruses. 3.       extended periods (at least 60 to 90minutes), being limited by the stability of the fluorescent ligand or receptor and protein matters (for the rotation to be slowed), not the distance between the protein, donor and acceptor

Watch Episode 167 Some GPCR-targeting antibodies don’t inhibit receptors. They activate them. Tom Sakmar points to a largely overlooked mechanism  in disease: autoantibodies that don’t block receptors “Some of these antibodies actually activate the receptor and cause pathological signaling.” — Tom Sakmar Luminex assay , researchers can now: Screen patient samples for GPCR autoantibodies Identify which receptor

Fluorescent ligands based on small molecules bind to the functional sites of receptors in live cells, This facilitates the study of receptor dynamics, ligand binding and signaling in real time. No need for fixation and permeabilization This step can modify receptor conformation and affect downstream , analyzing ligand-receptor interactions, which are not as detectable with antibodies. and CELT-483 for the hσ1/σ2 sigma receptor.

The central role of GPCRs in Neurological Disorders GPCRs are the largest family of membrane receptors One of the biggest hurdles is the understanding and correct targeting of the different receptor subtypes GPCR signaling: (A) an orthosteric ligand (orange) binds an inactive GPCR, the β2 adrenergic receptor Orphan G protein-coupled receptors: The role in CNS disorders . A Robust and Efficient FRET-Based Assay for Cannabinoid Receptor Ligands Discovery.

State transitions of coupled Gi-protein: Insights into internal water channel dynamics within dopamine receptor silico submolecular analyses Joseph Crecelius , Adriano Marchese , et al. for their excellent work on Receptor determinants for ß-arrestin functional specificity at C-X-C chemokine receptor 5 (CXCR5) Panjamaporn and β2 adrenergic receptors Receptor determinants for ß-arrestin functional specificity at C-X-C chemokine within dopamine receptor D3 from in silico submolecular analyses GPCRs in Cardiology, Endocrinology,

These probes facilitate localization of receptors, tracking of their internalization and are also safer activation dynamics, ligand binding geometry and receptor interactions.   fluorescent antagonist and CELT-095 hM1/M2 muscarinic receptor fluorescent antagonist). What are the current trends in G protein-coupled receptor targeted drug discovery? Portraying G protein-coupled receptors with fluorescent ligands.

The goal is to accelerate receptor-targeted discovery. It highlights its journey from one receptor to a cross-family toolkit. Hear from Drs. GPR45 steps up: A previously orphan receptor emerges as a powerful target for appetite and obesity control

rational drug discovery campaign hinges on a deep understanding of how distinct molecules interact with receptors Furthermore, data on the role of specific residues within receptors can provide valuable insights for specific ligand interactions, such as those at the adenosine A 1  adenosine receptor (Nguyen et al., G-protein coupled receptors: models, mutagenesis, and drug design. Structure-based discovery of A2A adenosine receptor ligands.

András Tóth, László Hunyady, et al. for their work on G protein-coupled receptor endocytosis generates Laurent Prézeau, for their research on Heterodimers revolutionize the field of metabotropic glutamate receptors by PAF Heterodimers revolutionize the field of metabotropic glutamate receptors Molecular Basis of MC1R SUCNR1 G protein-coupled receptor endocytosis generates spatiotemporal bias in β-arrestin signaling may prevent pancreatic cancer and agonists of angiotensin II type 2 receptor may prevent colorectal

GPCR, the global knowledge hub for G protein-coupled receptor (GPCR) research and education, is proud “These tools can dramatically improve how scientists measure ligand-receptor interactions, visualize partnership will help accelerate the adoption of our chemical tools and foster collaborations that turn receptor GPCR allows us to engage with researchers worldwide who are shaping the future of receptor-targeted therapies GPCR empowers scientists and companies advancing receptor biology and drug discovery.

Think a drug just "locks into" a receptor and does its job? Think again. It explains how the concentration of a drug influences its binding to the receptor. Instead, it involves a dynamic interaction between the drug and the receptor. The receptor may change shape upon binding, affecting how the drug interacts and how effective it will Understanding the intricate details of drug-receptor interactions transforms how we approach pharmacology

Administration (FDA) for use in adults for the management of acute pain severe enough to require an intravenous opioid

Most drugs don’t fail at the receptor level—they fail before they even reach it. In every lab, candidates fail not because they lack potency at a receptor, but because they stumble at Before your GPCR ligand ever meets its receptor, it meets the enzymes that determine whether it survives Even the most elegant GPCR ligand can fail if it never reaches its receptor. You’re not just designing for receptor activity—you’re designing for enzyme survival.

G protein-coupled receptors (GPCRs) are integral to cellular signaling, influencing a wide array of physiological The researchers found that certain GPCRs, such as vasopressin receptors, were expressed in hematopoietic For instance, the expression of specific chemokine receptors in monocytes and macrophages indicates their The current study found that 133 of these receptors were also detected, highlighting the robustness of However, the study also noted discrepancies, with 26 receptors identified in the previous study not detected

Adenine-derived scaffolds enabled selective adenosine receptor antagonists; tryptophan modifications led to somatostatin receptor ligands.  The molecule, not the receptor, becomes the guiding principle. Does it interact with the receptor in a way that biology can use? Core message: The receptor is only half the story. The molecule is the other half.

CXV: The Class F of G Protein-Coupled Receptors Yusman Manchanda, Dr. Molecular insights into orphan G protein-coupled receptors relevant to schizophrenia Single nucleotide variations encoding missense mutations in G protein-coupled receptors may contribute to autism GPCRs Unravelling G protein-coupled receptor signalling networks using global phosphoproteomics Reviews, GPCRs CXV: The Class F of G Protein-Coupled Receptors Structural and Molecular Insights into GPCR Function

GPCR contributor article Canonical chemokine receptors as scavenging “decoys” Shivani Sachdev, Brendan Bouvier, Jana Selent, et al. for their study on G protein-specific mechanisms in the serotonin 5-HT2A receptor function, impacting synaptic transmission Orphan receptor GPR88 as a potential therapeutic target for genome sequence analysis in India Methods & Updates in GPCR Research Engineering G protein-coupled receptors Phase 2a Obesity Study and Capsule to Tablet PK Study for its Oral Non-Peptide Small Molecule GLP-1 Receptor

In the case of fluorescent ligands , where a fluorescent tag is attached to a pharmacophore , the receptor This provides flexibility in labelling the GPCRs but may interfere with functional activity of the receptors If the experiment is done on live cells , tracking real-time receptor internalization becomes possible On the other hand, in fixed cells studies, it facilitates the structural context necessary to map receptor A Robust and Efficient FRET-Based Assay for Cannabinoid Receptor Ligands Discovery.

Hodson’s work with a major scientific wave: The rise of incretin-based therapies, especially GLP-1 receptor Receptor localization, ligand access, and intracellular signaling can look different in actual tissues For real translational understanding, you need to see  the receptor in context. Emerging direction: Genetics + receptor-distribution mapping. The next breakthroughs will come not from new receptors , but new ways of engaging and combining the

G protein-coupled receptors (GPCRs) are a vast family of membrane-bound proteins crucial for transmitting These receptors typically engage specific G protein subtypes, such as Gs, Gi/o, Gq/11, and G12/13, at Using BRET based approaches, the Gs-coupled vasopressin V2 receptor (V2R) was shown to form a stable Okashah, N., et al., Agonist-induced formation of unproductive receptor-G(12) complexes.  Stallaert, W., et al., Purinergic Receptor Transactivation by the β(2)-Adrenergic Receptor Increases

Jürgen Wess and Liu Liu for their study on A novel function of the M2 muscarinic receptor Drs. Zhan-Guo Gao, Mansour Haddad, and Kenneth A Jacobson for their work on A2B adenosine receptor signaling for breast cancer GPCR Activation and Signaling The TAS1R2 G-protein-coupled receptor is an ambient Kinetic Model for the Desensitization of G Protein-Coupled Receptor RNA-seq screening and gene function variants in the hypothalamic-pituitary-gonadal axis1 A novel function of the M2 muscarinic receptor

changes to clarify the molecular mechanisms governing ligand efficacy and potency at the β2 adrenergic receptor For example, orthosteric drug design —in which drugs bind to the receptor’s primary active site—can now be optimised by targeting specific ligand-receptor interactions to modify efficacy and potency. Allosteric modulators offer a promising approach for developing drugs that enhance or inhibit receptor Molecular basis of proton-sensing by G protein-coupled receptors. bioRxiv .

Azietaku , our great contributor, for his article Class B1 GPCR Dimerization: Unveiling Its Role in Receptor variant in RGS18 candidate for a familial mild bleeding syndrome Fusarium graminearum Ste2 and Ste3 Receptors Heterodimerization when Expressed Heterologously in Saccharomyces cerevisiae The beta 2 adrenergic receptor Neuronal Precursor Cells Derived from Patients Diagnosed with Schizophrenia Sphingosine 1-phosphate receptor the CaSR gene Reviews, GPCRs, and more Insight into structural properties of viral G protein-coupled receptors