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Electron cryo-microscopy (cryo-EM) is a powerful technique for the structural characterization of biological macromolecules, enabling high-resolution analysis of targets once inaccessible to structural interrogation. In recent years, pharmaceutical companies have begun to utilize cryo-EM for structure-based drug design. Structural analysis of integral membrane proteins, which comprise a large proportion of druggable targets and pose particular challenges for X-ray crystallography, by cryo-EM has enabled insights into important drug target families such as G protein-coupled receptors (GPCRs), ion channels, and solute carrier (SLCs) proteins. Structural characterization of biologics, such as vaccines, viral vectors, and gene therapy agents, has also become significantly more tractable. As a result, cryo-EM has begun to make major impacts in bringing critical therapeutics to market. In this review, we discuss recent instructive examples of impacts from cryo-EM in therapeutics design, focusing largely on its implementation at Pfizer. We also discuss the opportunities afforded by emerging technological advances in cryo-EM, and the prospects for future development of the technique. Read full article

Apart from G proteins, GPCRs engage other effectors for signaling modulation. receptor internalization. β-Arrestins facilitate this process by interacting with adapter protein 2 (AP This approach reveals binding interfaces and interactions between GPCRs and β-arrestins, paving the way This includes proteins like AP-2 and clathrin, vital for internalization, as well as MAPK cascade kinases

October 2022 High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal Together, these results link the morphogenetic effects of HH to the apico-basal distribution of SMO and

Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor (GPCR) that is defined as a regulator of appetite In addition to its function about weight gain and appetite control mechanisms of MC3R, recent studies point out the importance of the MC3R regulations in three main concepts: 1) its impact on weight and appetite

Mechanism of enhanced sensitivity of mutated β-adrenergic-like octopamine receptor to amitraz in honeybee Apis insecticides for effective control of pest infestation of Varroa destructor mite, a devastating parasite of Apis

He has led teams that have filed more than 10 Investigational New Drug Applications (IND), as well as multiple New Drug (NDA) and Supplemental New Drug Applications (SNDA). #biotech #lifesciences #appointment #GPCR #Oncology" Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Background: Uncoupling proteins (UCPs) are unpaired electron carriers that uncouple oxygen intake by the electron transport chain from ATP production in the inner membrane of the mitochondria. The physiological activities of UCPs have been hotly contested, and the involvement of UCPs in the pathogenesis and progression of diabetes mellitus is among the greatest concerns. UCPs are hypothesised to be triggered by superoxide and then reduce mitochondrial free radical production, potentially protecting diabetes mellitus patients who are experiencing oxidative stress. Objectives: The objectives of the study are to find out the newest ways to treat diabetes mellitus through protein uncoupling." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Research on cancer therapies focuses on processes such as angiogenesis, cell signaling, stemness, metastasis, and drug resistance and inflammation, all of which are influenced by the cellular and molecular microenvironment of the tumor. Different strategies, such as antibodies, small chemicals, hormones, cytokines, and, recently, gene editing techniques, have been tested to reduce the malignancy and generate a harmful microenvironment for the tumor. Few therapeutic agents have shown benefits when administered alone, but a few more have demonstrated clear improvement when administered in combination with other therapeutic molecules. In 2008 (and for the first time in the clinic), the therapeutic benefits of the β-adrenergic receptor antagonist, propranolol, were described in benign tumors, such as infantile hemangioma. Propranolol, initially prescribed for high blood pressure, irregular heart rate, essential tremor, and anxiety, has shown, in the last decade, increasing evidence of its antitumoral properties in more than a dozen different types of cancer. Moreover, the use of propranolol in combination therapies with other drugs has shown synergistic antitumor effects. This review highlights the clinical trials in which propranolol is taking part as adjuvant therapy at single administration or in combinatorial human trials, arising as a good pick and roll partner in anticancer strategies." Read more at the source #DrGPCR #GPCR #IndustryNews

later shape how he designed fluorescent probes, how he evaluated biological constraints, and how he approached performed consistently, JB and collaborators shifted toward a more rigorous parallelized screening approach probe design, multiplex fluorescent strategies that allow visualization of multiple GPCRs at once, and approaches

Help us reach more scientists by providing quick rating on Spotify or Apple Podcasts — and a YouTube Spotify: https://open.spotify.com/show/1KQHbC2qhkRIrdgBDtiQVF Apple Podcasts: https://podcasts.apple.com

They have to guess why it matters, what the application is, and whether it fits. ✅ Start with relevance It shows you’ve made deliberate choices about application, indication, or customer. 2️⃣ Why it matters Make it easy for the listener to understand what sets your approach apart from existing solutions or

And they avoid the costly surprises that appear when in vitro conclusions collide with human physiology Kenakin revealed  practical ways to anticipate these system-level interactions before they appear as High-coupled systems inflate apparent efficacy; low-coupled systems expose its limits. Dr. A partial agonist appears neutral until expression or coupling is increased. Dr. A compound may appear benign with one substrate and problematic with another.

These tools didn’t appear because someone wrote “visualize GPCRs better” in a grant. They appeared because one lab’s bottleneck became another lab’s engineering challenge — and together,

The Phases of a Reliable HCS Workflow Designing a robust HCS assay requires a structured, iterative approach This approach improves readout clarity, strengthens data reproducibility, and enables kinetic or equilibrium

. 👉 We’re talking about the type of quiet misalignment that appears to be progress but feels like confusion

depends on which cells express the receptor Side effects are tied to where agonists bind Weight-loss and appetite

The work introduced him to hormonal signaling, appetite regulation, and cellular communication systems

Insights into applying it to partial, inverse, and hemi-equilibrium systems. Schild analysis still applies—if used carefully. It sharpens interpretation—distinguishing real affinity  from apparent effect.

Use the four canonical criteria to distinguish genuine orthosteric antagonism from apparent shifts that Apply dose-ratios and Schild regressions to derive Kᴮ or pA₂ values that won’t collapse under scrutiny

These instincts are critical in the lab, but they often undermine leadership when blindly applied in

This ecosystem design blueprint applies to biotech teams and academic consortia alike.

Innovative Approaches in GPCR Drug Discovery: Designing Precise Solutions for GPCR Challenges.

Advances in chemoinformatics  introduced large-scale similarity mapping, such as SEA (Similarity Ensemble Approach This approach reveals: Hidden target overlap New therapeutic hypotheses “Off-target” effects that may

access program for researchers in developing countries  continues as well: eligible scientists can apply Our partnerships with Celtarys Research  and Revvity are great examples — uniting innovation and application We’ll share how to apply — and the details — soon. Community and Connection Dr. With appreciation and excitement, Yamina Berchiche Founder & CEO, Dr. GPCR About Dr. GPCR Dr.

Professor of Computational Biochemistry at Uppsala University and one of the strongest advocates for an approach In practice, this approach saves companies time, resources, and credibility with investors. Lessons from the Collaboration Blueprint Carlsson’s approach offers lessons across the spectrum of GPCR Why His Model Works What sets Carlsson apart is not just access to computational power or assay platforms It is the values he applies to every collaboration .

Nearly one-third of all approved drugs target them. The “Predict, Not Explain” Ethos What sets the Carlsson lab apart is its internal rule : results must

action for new GPCR ligands Elements of a comprehensive and effective GPCR discovery Master advanced applications

For Carlsson, this marked a shift in how his lab approached GPCR research. The division of labor reflects a pragmatic approach to problem-solving. Embracing Complexity and Failure Carlsson’s approach to modeling is rooted in scientific humility. shows that failures can evolve into strengths and that computational insights can transform how we approach

mice Orphan GPCRs in Neurodegenerative Disorders: Integrating Structural Biology and Drug Discovery Approaches

GPR45 steps up: A previously orphan receptor emerges as a powerful target for appetite and obesity control