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

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

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

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

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Through either random or targeted (site-directed) approaches, mutagenesis can provide a comprehensive

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on Design, Synthesis, and Characterization of New δ Opioid Receptor-Selective Fluorescent Probes and Applications Research Design, Synthesis, and Characterization of New δ Opioid Receptor-Selective Fluorescent Probes and Applications

Application of this knowledge to determine the mechanism of action of new GPCR ligands. Optimization of Candidate Selection Dates:  October 3rd to 31st, 2024 Registrants will learn: The powerful applications exploration of 4(α-l-rhamnosyloxy)-benzyl isothiocyanate: A promising phytochemical-based drug discovery approach

Submit your abstract today; the deadline is fast approaching! acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress Two C-terminal isoforms of Aplysia Descriptive molecular pharmacology of the δ opioid receptor (DOR): A computational study with structural approach

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Insights into GPCR Function Structural perspectives on chemokine receptors Industry News Exscientia Appoints

Using BRET based approaches, the Gs-coupled vasopressin V2 receptor (V2R) was shown to form a stable mechanisms underlying this phenomenon could unveil new dimensions of GPCR functionality and offer innovative approaches

protein-biased allosteric modulator of cannabinoid receptor CB1 GPCR function in autophagy control: a systematic approach

transmission Orphan receptor GPR88 as a potential therapeutic target for CNS disorders - an in silico approach GRN knockdown regulates the expression and alternative splicing of genes associated with aphasia-related for its Oral Non-Peptide Small Molecule GLP-1 Receptor Agonist GSBR-1290 Crinetics Pharmaceuticals Appoints

In humans there are approximately 45 chemokines, 19 chemotactic or G-protein coupled chemokine receptors

mating pathway Reviews, GPCRs, and more Highlights and hot topics in GPCR research from 'Down Under' Apelin Present Preclinical Data from GPCR Drug Discovery Engine at ENDO 2024 The Promise of Oxytocin: Novel Approaches