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Results found for "Stephen S G Ferguson"
- Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas ...
Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors
- Pharmacologic Models
Are you ready to truly understand how pharmacologists predict whole-body drug response from a single experiment? Terry Kenakin’s newest foundational lesson in Terry's Corner cuts straight to it: Why models are vital for translating lab data into clinical forecasts The 4 types of pharmacologic models (and when to use each) The truth about linear models: useful or misleading? How the Mass Action Law underpins nearly every model Future of Receptor Theory: Linkage vs. Probability Models This is practical drug development expertise from Terry’s 40+ years of experience. Beyond the lessons, Terry's Corner is your exclusive gateway. Ecosystem Premium Members: Look for significant savings on this and other resources in your weekly Dr. GPCR News. Elevate your pharmacology expertise. Unlock "Pharmacologic Models" now
- GPCR Drug Discovery at Discovery on Target: Why This Track Is About More Than Receptors
Join Dr. GPCR and global experts at the GPCR Drug Discovery session during Discovery on Target 2025—where groundbreaking collaborations begin. GPCR Drug Discovery at Discovery on Target 2025 — The Track You Can’t Miss If you work in drug discovery or biotech , this is your moment. Mark your calendar, it's happening September 22-25, 2025. From obesity and diabetes to cancer, fibrosis, and CNS disorders — GPCRs are at the heart of the world’s most pressing therapeutic challenges. And at this year’s Discovery on Target meeting in Boston, the GPCR Drug Discovery track will deliver breakthroughs, bold ideas, and the strategies shaping the next wave of medicines . I’m honored to be chairing a session in this track — with none other than Terry Kenakin on the speaker lineup. 🌟 Speaker Spotlight In the run-up to the conference, our founder Yamina Berchiche is speaking with some of the brilliant minds presenting in the GPCR track. Here’s who we've talked to so far: 🎥 Check out the interview with Dr. Aaron McGrath from Takeda 🎥 Interview with Kris Borzilleri & Alison Heick Varghese from Pfizer 🎥 Interview with Terry Kenakin from UNC and Terry's Corner We'll continue to update this section as new videos are released — so check back before the meeting for fresh insights and behind-the-scenes perspectives from our speakers. 🌐 Why Dr. GPCR Is in This Conversation At Dr. GPCR , our mission is simple: connect the GPCR community, share knowledge, and accelerate innovation . At Yamina's Corner , our founder Yamina Berchiche works closely with organizations to help them navigate receptor pharmacology, identify opportunities, and move their programs forward effectively. Over the years, we’ve built a global network of researchers, biotech leaders, and pharma innovators who believe that GPCR science is one of the most powerful tools we have to address urgent health challenges. Chairing this session isn’t just another speaking engagement — it’s an extension of what we do every day: Spotlight innovation across academia and industry. Foster collaboration through our platform and events. Push the boundaries of receptor pharmacology and its real-world applications. When we step into the GPCR track at Discovery on Target, we’re not just participating. We’re helping shape the conversation. 🚀 Why GPCRs Are Still the Hottest Target Class in Drug Discovery GPCRs regulate countless physiological processes, making them a goldmine for therapeutic breakthroughs. They’re already behind blockbuster drugs: GLP-1 receptor agonists – reshaping obesity & type 2 diabetes care. CCR5 antagonists – fighting HIV and certain cancers. Dopamine D2 receptor modulators – transforming treatment for Parkinson’s & schizophrenia. PAR1 antagonists – protecting cardiovascular health. But the real excitement is in what’s next: Biased signaling for selective therapeutic effects. Allosteric modulation for unprecedented precision. Structure-based design powered by cryo-EM and AI. 🔬 Inside the GPCR Track Agenda Expect deep dives into: CXCR4 in oncology and immune regulation. GIPR/GLP-1R co-agonists in metabolic diseases. Serotonin & dopamine receptor modulation for neuropsychiatric disorders. Orphan GPCRs with untapped therapeutic potential. These sessions bridge structural biology , computational modeling , and clinical translation — with tangible takeaways for programs from discovery through late-stage development. 🗝️ Highlight: Terry Kenakin at Discovery on Target Terry Kenakin’s work on functional selectivity has transformed GPCR drug discovery, showing how to bias receptor signaling toward beneficial outcomes and away from side effects. Hearing Terry speak is more than an academic experience — it’s like being handed a new set of tools to rethink your drug design strategy. Having him in the session I’m chairing is not just an honor — it’s a highlight of the year. 📚 Terry’s Corner — The Only On-Demand Pharmacology Hub with Dr. Kenakin Himself If you’re part of the Dr. GPCR community, you already know about Terry’s Corner — our exclusive, on-demand pharmacology series where Terry Kenakin breaks down receptor pharmacology, functional selectivity, and ligand bias in a way you can apply directly to your work. It’s the only resource of its kind — part masterclass, part fireside chat — available anytime to our members. For those who can’t get enough of Terry’s insights at Discovery on Target, Terry’s Corner keeps the learning going long after the conference ends. 💡 Why This Matters — Even If You’re Not a GPCR Scientist GPCR pathways intersect with oncology, CNS, metabolic, cardiovascular, immunology, and fibrosis research . Whether you’re in early discovery or clinical development, the strategies here could open doors in your own therapeutic area. 🧭 Join Us in Boston 🗓 Discovery on Target — Boston, MA 📅 September 23-25, 2025 🎯 Track: GPCR Drug Discovery Let’s connect. Let’s debate. Let’s move GPCR drug discovery forward — together. 🚨 Mark your calendar for the GPCR Happy Hour Join us at GPCR Happy Hour , where scientists, biotech leaders, CRO professionals, and investors from around the globe meet Boston’s vibrant life sciences hub. ✨ Spark collaborations. ✨ Strengthen the GPCR community. ✨ Be part of Dr. GPCR’s nonprofit mission to connect and empower the global GPCR ecosystem. 📅 September 24, 2025 📍 Pressed Café, Huntington Ave, Boston ⏰ 6–8 PM EST ⚠️ Space is limited — Secure your spot now
- Constitutive, Basal, and β-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled ..
Constitutive, Basal, and β-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor D Induces Release of the Inflammatory Cytokine IL-6 and Is Dependent on NF-κB Signaling G protein-coupled Members of the Mas-related G protein coupled receptors (MRGPRs), a subfamily of GPCRs, are largely expressed However, involvement of the human Mas-related G-protein coupled receptor D (MRGPRD) in the regulation
- Accelerating GPCR Drug Discovery
Why I Started GPCR Consulting You've got great data. You've got brilliant scientists. But your GPCR program still isn't moving at the pace it should. I've seen this pattern unfold across biotech, academia, and nonprofits. The assays are running, data is flowing in from your CROs or your internal labs , yet progress stalls. Decisions are slow, crucial data is siloed, and despite everyone working hard, programs drift. For over two decades, my work has centered on GPCR pharmacology . In every role and sector, I found myself drawn to the same critical challenges: missed opportunities, misaligned systems, and promising programs stalling despite strong science. I was always the one identifying what could be improved: The essential structure that was missing. The clarity that was desperately lacking. The unnecessary friction that slowed everything down. Traditional roles rarely gave me the freedom to implement these changes at the scale needed. So, I created a new path—one that allows me to embed, optimize, and accelerate GPCR programs from the inside out. The GPCR Data Dilemma: The Lego Bucket Problem I've seen promising GPCR programs generate massive volumes of high-quality data. But without structure, it's just a messy pile of colored blocks. I call this the Lego Bucket Problem . You have the data, but not the definitive direction. This disconnect frequently leads to: Underperforming assays. Internal data and CRO outputs misaligned with strategic goals. Delays in critical go/no-go decisions. Frustrated teams and slipping timelines. It's not just a scientific issue—it's an operational one. You can't move fast without clarity, and you can't make confident decisions without robust structure. My Approach: Biology, Execution, Systems My consulting approach uniquely blends deep pharmacology expertise with the operational discipline required to make that expertise actionable. Here's how I bring a fresh perspective: Biology-First, Data-Driven Strategy: I help you focus on the science that truly matters. We cut through the noise, elevate what's working, and strategically solve what's not, ensuring your GPCR program stays on target. Embedded Execution: I work alongside your team—not above it. I'll help write CRO scopes, meticulously review assay data, flag risks early, and keep your programs relentlessly on track. Systems That Drive Progress: From assay tracking to data workflows, I design simple, scalable tools that surface insights early and dramatically reduce delays, transforming your data into actionable intelligence. A Broader Lens: Dr. GPCR As the co-founder of Dr. GPCR, we've built a global hub connecting over 1,300 GPCR scientists dedicated to this field. These ongoing conversations keep me on the front lines, sharpening my understanding of the common bottlenecks and evolving needs across the entire GPCR community. My Consulting Philosophy This practice is built on three core values: Scientific Integrity: Every recommendation is grounded in real-world evidence and extensive experience. Operational Discipline: Robust systems and clear structure aren't "nice to have"—they are absolutely essential for efficient progress. Collaborative Partnership: I embed, contribute, and build solutions hand-in-hand with your team. Ready to Move Your GPCR Program Forward? If you're navigating a stuck GPCR program, planning your next crucial milestone, or struggling to gain clarity from complex data, I'd love to help. 📌 Learn more about my services: Yamina.org 📅 Book a 30-minute strategy call: https://calendly.com/drgpcr/yamina-corner
- A cryptic mode of GPCR regulation revealed
October 2022 "Over three decades of research have provided thorough insights into G protein-coupled receptor Agonist activation of the β2-adrenoceptor (β2AR) causes its S-nitrosylation that is required for the Eliminating β2AR S-nitrosylation by mutation of C265 augments β2AR protein kinase A signaling, enables
- Single-molecule counting applied to the study of GPCR oligomerization
Consider G-protein-coupled receptors-an expansive class of transmembrane signaling proteins that participate on the potential for these techniques to advance our understanding of the role of oligomerization in G-protein-coupled
- Structural basis of GPCR coupling to distinct signal transducers: implications for biased signaling
August 2022 "Three classes of G-protein-coupled receptor (GPCR) partners - G proteins, GPCR kinases,
- Interacting binding insights and conformational consequences of the differential activity of...
conformational consequences of the differential activity of cannabidiol with two endocannabinoid-activated G-protein-coupled to modulate different receptors in the endocannabinoid system, some of which belong to the family of G-protein-coupled investigate the interacting determinants of CBD in two closely related endocannabinoid-activated GPCRs, the G-protein-coupled
- Structure-Based Discovery of Negative Allosteric Modulators of the Metabotropic Glutamate Receptor 5
October 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed
- Activation of GPR183 by 7 α,25-Dihydroxycholesterol Induces Behavioral Hypersensitivity through...
through Mitogen-Activated Protein Kinase and Nuclear Factor- κ B "Emerging evidence implicates the G-protein
- Successful prednisolone or calcimimetic treatment of acquired hypocalciuric hypercalcemia caused...
This emphasizes the importance of the Gi/o (pertussis toxin-sensitive G proteins, whose βγ subunits activate (f) the presence of CaSR autoantibodies that operated as biased allosteric modulators of CaSR, and (g)
- New structural perspectives in G protein-coupled receptor-mediated Src family kinase activation
Excited to hear Dr. Sandra Berndt talk about new structural perspectives in GPCR-mediated Src family kinase activation. Register here (FREE) https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe #drgpcr #gpcr #virtualcafe
- Dr. Alexander S. Hauser receives the Bachem award for peptide science
November 2021 Read more at the source #DrGPCR #GPCR #IndustryNews
- Comparative studies of AlphaFold, RoseTTAFold and Modeller: a case study involving the use of...
2022 Comparative studies of AlphaFold, RoseTTAFold and Modeller: a case study involving the use of G-protein-coupled G-protein-coupled receptor (GPCR) proteins are particularly interesting since they are involved in numerous
- Structural basis for receptor selectivity and inverse agonism in S1P5 receptors
September 2022 "The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors (S1PRs) - S1P1-5. S1P5 is predominantly expressed in nervous and immune systems, regulating the egress of natural killer cells from lymph nodes and playing a role in immune and neurodegenerative disorders, as well as carcinogenesis. Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor subtype selectivity, which leads to side effects. In this article, we describe a 2.2 Å resolution room temperature crystal structure of the human S1P5 receptor in complex with a selective inverse agonist determined by serial femtosecond crystallography (SFX) at the Pohang Accelerator Laboratory X-Ray Free Electron Laser (PAL-XFEL) and analyze its structure-activity relationship data. The structure demonstrates a unique ligand-binding mode, involving an allosteric sub-pocket, which clarifies the receptor subtype selectivity and provides a template for structure-based drug design. Together with previously published S1PR structures in complex with antagonists and agonists, our structure with S1P5-inverse agonist sheds light on the activation mechanism and reveals structural determinants of the inverse agonism in the S1PR family." Read more at the source #DrGPCR #GPCR #IndustryNews
- The regulation of PKA signaling in obesity and in the maintenance of metabolic health
PKA facilitates the actions of hormones, neurotransmitters and other signaling molecules that bind G-protein
- Isoforms of GPR35 have distinct extracellular N-termini that allosterically modify...
receptor-transducer coupling and mediate intracellular pathway bias "Within the intestine, the human G isoforms for constitutive and ligand-induced activation and signaling of 10 different heterotrimeric G Our results reveal that the extended N-terminus of the long isoform limits G protein activation yet elevates
- Function and structure of bradykinin receptor 2 for drug discovery
October 2022 "Type 2 bradykinin receptor (B2R) is an essential G protein-coupled receptor (GPCR) that
- Mechanistic Understanding of the Palmitoylation of Go Protein in the Allosteric Regulation of...
the Palmitoylation of Go Protein in the Allosteric Regulation of Adhesion Receptor GPR97 "Adhesion G-protein-coupled
- Case Report of a Juvenile Patient with Autism Spectrum Disorder with a Novel Combination of Copy...
One of the CNVs is located on chromosome 4q13.1 in the region of the gene encoding for adhesion G protein-coupled
- GPR108 is required for gambogic acid inhibiting NF-κB signaling in cancer
September 2022 "GPCRs are the most potential targets for drug discovery, however, their role in oncology is underappreciated and GPCR-based anti-cancer drug is not fully investigated. Herein, we identified GPR108, a GPCR protein described in innate immune system, is a potential therapeutic target of cancer. Depletion of GPR108 dramatically inhibited the survival of various cancers. Notably, TNFα activation of NF-κB was totally impaired after GPR108 knockout. We identified gambogic acid (GA), a natural prenylated xanthone, selectively targeting GPR108. Importantly, GA engaged with GPR108 and promoted its degradation, knockout of GPR108 remarkably blocked GA inhibition of NF-κB signaling. Furthermore, in vitro and in vivo assays demonstrated that GA was dependent on GPR108 to exert anti-cancer activity. Overall, our findings supported GPR108 as a promising therapeutic target of cancer, and provided a small molecule inhibitor GA directly and selectively targeting GPR108 for cancer therapy." Read more at the source #DrGPCR #GPCR #IndustryNews
- Coordinated transcriptomics and peptidomics of central nervous system identify neuropeptides and ...
Coordinated transcriptomics and peptidomics of central nervous system identify neuropeptides and their G Neuropeptides and their specific receptors (primarily G protein-coupled receptors, GPCRs) regulate multiple Here, we generated a transcriptome of the central nervous system (CNS) of G. molesta. Using peptidomic analysis of CNS of G. molesta, we identified total of 28 mature peptides and precursor-related determine physiological functions and pharmacological characterization of neuropeptides and their GPCRs in G.
- Mechanistic basis of GPCR activation explored by ensemble refinement of crystallographic structures
October 2022 "G protein-coupled receptors (GPCRs) are important drug targets characterized by a canonical
- Allosteric modulation of GPCRs: From structural insights to in silico drug discovery
October 2022 "G protein-coupled receptors (GPCRs) play critical roles in human physiology and are one
- Coincident Regulation of PLCβ Signaling by Gq-Coupled and μOpioid Receptors Opposes Opioid- Mediated
October 2022 Coincident Regulation of PLCβ Signaling by Gq-Coupled and μOpioid Receptors Opposes Opioid- Mediated Antinociception "Pain management is a significant problem worldwide. The current frontline approach for pain-management is the use of opioid analgesics. The primary analgesic target of opioids is the μ-opioid receptor (MOR). Deletion of phospholipase Cβ3 (PLCβ3), or selective inhibition of Gβγ regulation of PLCβ3, enhances the potency of the antinociceptive effects of morphine suggesting a novel strategy for achieving opioid sparing effects. Here we investigated a potential mechanism for regulation of PLC signaling downstream of MOR in HEK293 cells and found that MOR alone could not stimulate PLC, but rather required a coincident signal from a Gq coupled receptor. Knockout of PLCβ3, or pharmacological inhibition of its upstream regulators, Gβγ or Gq, ex vivo in periaqueductal gray (PAG) slices increased the potency of the selective MOR agonist DAMGO in inhibiting presynaptic GABA release. Finally, inhibition of Gq-GPCR coupling in mice enhanced the antinociceptive effects of morphine. These data support a model where Gq and Gβγ-dependent signaling cooperatively regulate PLC activation to decrease MOR-dependent antinociceptive potency. Ultimately this could lead to identification of new non-MOR targets that would allow for lower dose utilization of opioid analgesics. " Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Newsletter HERE
- Rescue of Cell Surface Expression and Signaling of Mutant Follicle-Stimulating Hormone Receptors
Mutations in G protein-coupled receptors (GPCRs) underlie numerous diseases.
- Use of CRISPR/Cas9-edited HEK293 cells reveals that both conventional and novel protein kinase C...
novel protein kinase C isozymes are involved in mGlu5a receptor internalization "The internalization of G
- Structural perspectives on the mechanism of signal activation, ligand selectivity and allosteric...
October 2022 Structural perspectives on the mechanism of signal activation, ligand selectivity and allosteric modulation in angiotensin receptors: IUPHAR Review 34 "Functional advances have guided our knowledge of physiological and fatal pathological mechanisms of the hormone angiotensin II (AngII) and its antagonists. Such studies revealed that tissue response to a given dose of the hormone or its antagonist depends on receptors that engage the ligand. Thus, we need to know much more about the structures of receptor-ligand complexes at high resolution. Recently, X-ray structures of both AngII receptors (AT1 and AT2 receptors) bound to peptide and non-peptide ligands have been elucidated, providing new opportunities to examine the dynamic fluxes in the 3D architecture of the receptors, as the basis of ligand selectivity, efficacy, and regulation of the molecular functions of the receptors. Constituent structural motifs cooperatively transform ligand selectivity into specific functions, thus conceptualizing the primacy of the 3D structure over individual motifs of receptors. This review covers the new data elucidating the structural dynamics of AngII receptors and how structural knowledge can be transformative in understanding the mechanisms underlying the physiology of AngII." Read more at the source #DrGPCR #GPCR #IndustryNews
- Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects Ca 2+ Sensing but...
Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects Ca 2+ Sensing but Not G Protein Interaction "The calcium-sensing receptor is a homodimeric class C G protein-coupled receptor senses extracellular Ca2+ (Ca2+o ) via a dimeric extracellular Venus flytrap (VFT) unit that activates G