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  • Targeting mGluR2/3 for treatment of neurodegenerative and neuropsychiatric diseases

    September 2022 "Glutamate is the primary excitatory neurotransmitter in the brain and plays critical roles in all aspects of neuronal function. Disruption of normal glutamate transmission has been implicated in a variety of neurodegenerative and neuropsychiatric diseases. Glutamate exerts its effect through ionotropic and metabotropic glutamate receptors (mGluRs). mGluR2 and mGluR3 are members of the Group II mGluR family and their activation leads to the inhibition of glutamate release from presynaptic nerve terminals and is also poised upstream of a myriad of signaling pathways in postsynaptic nerve terminals and neuroglia. Therefore, mGluR2 and mGluR3 have been considered as potential drug targets for the treatment of many neurological conditions and several compounds targeting these receptors have been developed. In this review, we discuss what is currently known regarding the contribution of mGluR2 and mGluR3 to the pathophysiology of some neurodegenerative and neuropsychiatric diseases including Amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's diseases, schizophrenia and depression as well as drug addiction. We then highlight the evidence supporting the use of various drugs including orthosteric and allosteric ligands acting on either mGluR2, mGluR3 or both for the management of these brain disorders." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Identification of hub genes in the subacute spinal cord injury in rats

    September 2022 "Background Spinal cord injury (SCI) is a common trauma in clinical practices. Subacute SCI is mainly characterized by neuronal apoptosis, axonal demyelination, Wallerian degeneration, axonal remodeling, and glial scar formation. It has been discovered in recent years that inflammatory responses are particularly important in subacute SCI. However, the mechanisms mediating inflammation are not completely clear. Methods The gene expression profiles of GSE20907, GSE45006, and GSE45550 were downloaded from the GEO database. The models of the three gene expression profiles were all for SCI to the thoracic segment of the rat. The differentially expressed genes (DEGs) and weighted correlation network analysis (WGCNA) were performed using R software, and functional enrichment analysis and protein–protein interaction (PPI) network were performed using Metascape. Module analysis was performed using Cytoscape. Finally, the relative mRNA expression level of central genes was verified by RT-PCR." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Endogenous ligand recognition and structural transition of a human PTH receptor

    September 2022 "Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects. The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation kinetics. Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the presence of PTH or PTHrP at resolutions of 2.8 -4.1 Å. A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP." Read more at the source #DrGPCR #GPCR #IndustryNews

  • CD28 and chemokine receptors: Signalling amplifiers at the immunological synapse

    September 2022 "T cells are master regulators of the immune response tuning, among others, B cells, macrophages and NK cells. To exert their functions requiring high sensibility and specificity, T cells need to integrate different stimuli from the surrounding microenvironment. A finely tuned signalling compartmentalization orchestrated in dynamic platforms is an essential requirement for the proper and efficient response of these cells to distinct triggers. During years, several studies have depicted the pivotal role of the cytoskeleton and lipid microdomains in controlling signalling compartmentalization during T cell activation and functions. Here, we discuss mechanisms responsible for signalling amplification and compartmentalization in T cell activation, focusing on the role of CD28, chemokine receptors and the actin cytoskeleton. We also take into account the detrimental effect of mutations carried by distinct signalling proteins giving rise to syndromes characterized by defects in T cell functionality." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes

    September 2022 "Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute to neuroplasticity regulation and are implicated in numerous neuronal disorders. Here, we demonstrate a physical interaction between 5-HT2A and TrkB in vitro and in vivo using co-immunoprecipitation and biophysical and biochemical approaches. Heterodimerization decreased TrkB autophosphorylation, preventing its activation with agonist 7,8-DHF, even with low 5-HT2A receptor expression. A blockade of 5-HT2A receptor with the preferential antagonist ketanserin prevented the receptor-mediated downregulation of TrkB phosphorylation without restoring the TrkB response to its agonist 7,8-DHF in vitro. In adult mice, intraperitoneal ketanserin injection increased basal TrkB phosphorylation in the frontal cortex and hippocampus, which is in accordance with our findings demonstrating the prevalence of 5-HT2A–TrkB heteroreceptor complexes in these brain regions. An expression analysis revealed strong developmental regulation of 5-HT2A and TrkB expressions in the cortex, hippocampus, and especially the striatum, demonstrating that the balance between TrkB and 5-HT2A may shift in certain brain regions during postnatal development. Our data reveal the functional role of 5-HT2A–TrkB receptor heterodimerization and suggest that the regulated expression of 5-HT2A and TrkB is a molecular mechanism for the brain-region-specific modulation of TrkB functions during development and under pathophysiological conditions." Read more at the source #DrGPCR #GPCR #IndustryNews

  • PAR-Induced Harnessing of EZH2 to β-Catenin: Implications for Colorectal Cancer

    September 2022 "G-protein-coupled receptors (GPCRs) are involved in a wide array of physiological and disease functions, yet knowledge of their role in colon cancer stem cell maintenance is still lacking. In addition, the molecular mechanisms underlying GPCR-induced post-translational signaling regulation are poorly understood. Here, we find that protease-activated receptor 4 (PAR4) unexpectedly acts as a potent oncogene, inducing β-catenin stability and transcriptional activity. Both PAR4 and PAR2 are able to drive the association of methyltransferase EZH2 with β-catenin, culminating in β-catenin methylation. This methylation on a lysine residue at the N-terminal portion of β-catenin suppresses the ubiquitination of β-catenin, thereby promoting PAR-induced β-catenin stability and transcriptional activity. Indeed, EZH2 is found to be directly correlated with high PAR4-driven tumors, and is abundantly expressed in large tumors, whereas very little to almost none is expressed in small tumors. A truncated form of β-catenin, ∆N133β-catenin, devoid of lysine, as well as serine/threonine residues, exhibits low levels of β-catenin and a markedly reduced transcriptional activity following PAR4 activation, in contrast to wt β-catenin. Our study demonstrates the importance of β-catenin lysine methylation in terms of its sustained expression and function. Taken together, we reveal that PAR-induced post-transcriptional regulation of β-catenin is centrally involved in colon cancer." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Endocannabinoid System in the Neuroendocrine Response to Lipopolysaccharide-induced Immune Challenge

    September 2022 "The endocannabinoid system plays a key role in the intersection of the nervous, endocrine, and immune systems, regulating not only their functions but also how they interplay with each other. Endogenous ligands, named endocannabinoids, are produced “on demand” to finely regulate the synthesis and secretion of hormones and neurotransmitters, as well as to regulate the production of cytokines and other proinflammatory mediators. It is well known that immune challenges, such as exposure to lipopolysaccharide, the main component of the Gram-negative bacteria cell wall, disrupt not only the hypothalamic–pituitary–adrenal axis but also affects other endocrine systems such as the hypothalamic–pituitary–gonadal axis and the release of oxytocin from the neurohypophysis. Here we explore which actors and molecular mechanisms are involved in these processes." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Isoform-and ligand-specific modulation of adhesion GPCR ADGRL3/Latrophilin3 by a synthetic binder

    September 2022 "Adhesion G protein-coupled receptors (aGPCRs) are cell-surface proteins with large extracellular regions that bind to multiple ligands to regulate key biological functions including neurodevelopment and organogenesis. Modulating a single function of a specific aGPCR isoform while affecting no other function and no other receptor is not trivial. Here, we engineered an antibody, termed LK30, that binds to the extracellular region of the aGPCR ADGRL3, and specifically acts as an agonist for ADGRL3 but not for its isoform, ADGRL1. The LK30/ADGRL3 complex structure revealed that the LK30 binding site on ADGRL3 overlaps with the binding site for an ADGRL3 ligand – teneurin. In cellular-adhesion assays, LK30 specifically broke the trans-cellular interaction of ADGRL3 with teneurin, but not with another ADGRL3 ligand – FLRT3. Our work provides proof of concept for the modulation of isoform- and ligand specific aGPCR functions using unique tools, and thus establishes a foundation for the development of fine-tuned aGPCR-targeted therapeutics" Read more at the source #DrGPCR #GPCR #IndustryNews

  • Arginine 125 Is an Essential Residue for the Function of MRAP2

    September 2022 "MRAP2 is a small simple transmembrane protein arranged in a double antiparallel topology on the plasma membrane. It is expressed in the paraventricular nucleus of the hypothalamus, where it interacts with various G protein-coupled receptors, such as the prokineticin receptors, and regulates energy expenditure and appetite. The aim of this work was to analyze the functional role of the specific arginine residue at position 125 of MRAP2, which affects protein conformation, dimer formation, and PKR2 binding. Results obtained with the MRAP2 mutants R125H and R125C, which are found in human patients with extreme obesity, and mouse MRAP2, in which arginine 125 is normally replaced by histidine, were compared with those obtained with human MRAP2. Understanding the mechanism by which MRAP2 regulates G protein-coupled receptors helps in elucidating the metabolic pathways involved in metabolic dysfunction and in developing new drugs as specific targets of the MRAP2-PKR2 complex." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Immunomodulatory Role of Neuropeptides in the Cornea

    September 2022 "The transparency of the cornea along with its dense sensory innervation and resident leukocyte populations make it an ideal tissue to study interactions between the nervous and immune systems. The cornea is the most densely innervated tissue of the body and possesses both immune and vascular privilege, in part due to its unique repertoire of resident immune cells. Corneal nerves produce various neuropeptides that have a wide range of functions on immune cells. As research in this area expands, further insights are made into the role of neuropeptides and their immunomodulatory functions in the healthy and diseased cornea. Much remains to be known regarding the details of neuropeptide signaling and how it contributes to pathophysiology, which is likely due to complex interactions among neuropeptides, receptor isoform-specific signaling events, and the inflammatory microenvironment in disease. However, progress in this area has led to an increase in studies that have begun modulating neuropeptide activity for the treatment of corneal diseases with promising results, necessitating the need for a comprehensive review of the literature. This review focuses on the role of neuropeptides in maintaining the homeostasis of the ocular surface, alterations in disease settings, and the possible therapeutic potential of targeting these systems." Read more at the source #DrGPCR #GPCR #IndustryNews

  • 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

  • Dynamics of tumor-associated macrophages in a quantitative systems pharmacology model of...

    September 2022 Dynamics of tumor-associated macrophages in a quantitative systems pharmacology model of immunotherapy in triple-negative breast cancer "Quantitative systems pharmacology (QSP) modeling is an emerging mechanistic computational approach that couples drug pharmacokinetics/pharmacodynamics and the course of disease progression. It has begun to play important roles in drug development for complex diseases such as cancer, including triple-negative breast cancer (TNBC). The combination of the anti-PD-L1 antibody atezolizumab and nab-paclitaxel has shown clinical activity in advanced TNBC with PD-L1-positive tumor-infiltrating immune cells. As tumor-associated macrophages (TAMs) serve as major contributors to the immuno-suppressive tumor microenvironment, we incorporated the dynamics of TAMs into our previously published QSP model to investigate their impact on cancer treatment. We show that through proper calibration, the model captures the macrophage heterogeneity in the tumor microenvironment while maintaining its predictive power of the trial results at the population level. Despite its high mechanistic complexity, the modularized QSP platform can be readily reproduced, expanded for new species of interest, and applied in clinical trial simulation." Read more at the source #DrGPCR #GPCR #IndustryNews

  • GPCR kinase phosphorylation of distal C-tail sites specifies βarrestin1-mediated signaling by...

    September 2022 "G protein-coupled receptor (GPCR) kinases (GRKs) and arrestins mediate GPCR desensitization, internalization, and signaling. The spatial pattern of GPCR phosphorylation is predicted to trigger these discrete GRK and arrestin-mediated functions. Here, we provide evidence that distal carboxyl-terminal tail (C-tail), but not proximal, phosphorylation of the chemokine receptor CXCR4 specifies βarrestin1 (βarr1)-dependent signaling. We demonstrate by pharmacologic inhibition of GRK2/3-mediated phosphorylation of the chemokine receptor CXCR4 coupled with site-directed mutagenesis and bioluminescence resonance energy transfer approaches that distal, not proximal, C-tail phosphorylation sites are required for recruitment of the adaptor protein STAM1 (signal-transducing adaptor molecule) to βarr1 and focal adhesion kinase phosphorylation but not extracellular signal-regulated kinase 1/2 phosphorylation. In addition, we show that GPCRs that have similarly positioned C-tail phosphoresidues are also able to recruit STAM1 to βarr1. However, although necessary for some GPCRs, we found that distal C-tail sites might not be sufficient to specify recruitment of STAM1 to βarr1 for other GPCRs. In conclusion, this study provides evidence that distal C-tail phosphorylation sites specify GRK-βarrestin-mediated signaling by CXCR4 and other GPCRs." Read more at the source #DrGPCR #GPCR #IndustryNews

  • The Impact of CB1 Receptor on Nuclear Receptors in Skeletal Muscle Cells

    September 2021 "Cannabinoids are abundant signaling compounds; their influence predominantly arises via engagement with the principal two G-protein-coupled cannabinoid receptors, CB1 and CB2. One suggested theory is that cannabinoids regulate a variety of physiological processes within the cells of skeletal muscle. Earlier publications have indicated that expression of CB1 receptor mRNA and protein has been recognized within myotubes and tissues of skeletal muscle from both murines and humans, thus representing a potentially significant pathway which plays a role in the control of skeletal muscular activities. The part played by CB1 receptor activation or inhibition with respect to these functions and relevant to targets in the periphery, especially skeletal muscle, is not fully delineated. Thus, the aim of the current research was to explore the influence of CB1 receptor stimulation and inhibition on downstream signaling of the nuclear receptor, NR4A, which regulates the immediate impacts of arachidonyl-2′-chloroethylamide (ACEA) and/or rimonabant in the cells of skeletal muscle. Murine L6 skeletal muscle cells were used in order to clarify additional possible molecular signaling pathways which contribute to alterations in the CB1 receptor. Skeletal muscle cells have often been used; it is well-documented that they express cannabinoid receptors. Quantitative real-time probe-based polymerase chain reaction (qRT-PCR) assays are deployed in order to assess the gene expression characteristics of CB1 receptor signaling. In the current work, it is demonstrated that skeletal muscle cells exhibit functional expression of CB1 receptors. This can be deduced from the qRT-PCR assays; triggering CB1 receptors amplifies both NR4A1 and NR4A3 mRNA gene expression. The impact of ACEA is inhibited by the selective CB1 receptor antagonist, rimonabant. The present research demonstrated that 10 nM of ACEA notably amplified mRNA gene expression of NR4A1 and NR4A3; this effect was suppressed by the addition of 100 nM rimonabant. Furthermore, the CB1 receptor antagonist led to the downregulation of mRNA gene expression of NR4A1, NR4A2 and NR4A3. In conclusion, in skeletal muscle, CB1 receptors were recognized to be important moderators of NR4A1 and NR4A3 mRNA gene expression; these actions may have possible clinical benefits. Thus, in skeletal muscle cells, a possible physiological expression of CB1 receptors was identified. It is as yet unknown whether these CB1 receptors contribute to pathways underlying skeletal muscle biological function and disease processes. Further research is required to fully delineate their role(s)." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Biased GPCR signaling by the native parathyroid hormone-related protein 1 to 141 relative to its...

    September 2022 Biased GPCR signaling by the native parathyroid hormone-related protein 1 to 141 relative to its N-terminal fragment 1 to 36 "The parathyroid hormone (PTH)-related protein (PTHrP) is indispensable for the development of mammary glands, placental calcium ion transport, tooth eruption, bone formation and bone remodeling, and causes hypercalcemia in patients with malignancy. Although mature forms of PTHrP in the body consist of splice variants of 139, 141, and 173 amino acids, our current understanding on how endogenous PTHrP transduces signals through its cognate G-protein coupled receptor (GPCR), the PTH type 1 receptor (PTHR), is largely derived from studies done with its N-terminal fragment, PTHrP1-36. Here, we demonstrate using various fluorescence imaging approaches at the single cell level to measure kinetics of (i) receptor activation, (ii) receptor signaling via Gs and Gq, and (iii) receptor internalization and recycling that the native PTHrP1-141 displays biased agonist signaling properties that are not mimicked by PTHrP1-36. Although PTHrP1-36 induces transient cAMP production, acute intracellular Ca2+ (iCa2+) release and β-arrestin recruitment mediated by ligand-PTHR interactions at the plasma membrane, PTHrP1-141 triggers sustained cAMP signaling from the plasma membrane and fails to stimulate iCa2+ release and recruit β-arrestin. Furthermore, we show that the molecular basis for biased signaling differences between PTHrP1-36 and properties of native PTHrP1-141 are caused by the stabilization of a singular PTHR conformation and PTHrP1-141 sensitivity to heparin, a sulfated glycosaminoglycan. Taken together, our results contribute to a better understanding of the biased signaling process of a native protein hormone acting in conjunction with a GPCR." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Opposite Effects of Src Family Kinases on YAP and ERK Activation in Pancreatic Cancer Cells...

    September 2022 Opposite Effects of Src Family Kinases on YAP and ERK Activation in Pancreatic Cancer Cells: Implications for Targeted Therapy "Pancreatic ductal adenocarcinoma (PDAC) remains an aggressive disease that is expected to become the second cause of cancer fatalities during the next decade. As therapeutic options are limited, novel targets and agents for therapeutic intervention are urgently needed. Previously, we identified potent positive crosstalk between insulin/IGF-1 receptors and G protein-coupled (GPCR) signaling systems leading to mitogenic signaling in PDAC cells. Here, we show that a combination of insulin and the GPCR agonist neurotensin induced rapid activation of Src family of tyrosine kinases (SFKs) within PANC-1 cells, as shown by FAK phosphorylation at Tyr576/577 and Tyr861, sensitive biomarkers of SFK activity within intact cells and Src419 autophosphorylation. Crucially, SFKs promoted YAP nuclear localization and phosphorylation at Tyr357, as shown by using the SFK inhibitors dasatinib, saracatinib, the preferential YES1 inhibitor CH6953755, short interfering RNA (siRNA)-mediated knockdown of YES1 and transfection of epitogue-tagged YAP mutants in PANC-1 and MiaPaCa-2 cancer cells, models of the aggressive squamous subtype of PDAC. Surprisingly, our results also demonstrate that exposure to SFK inhibitors, including dasatinib or knockdown of YES and Src induces ERK over-activation in PDAC cells. Dasatinib-induced ERK activation was completely abolished by exposure to the FDA-approved MEK inhibitor trametinib. A combination of dasatinib and trametinib potently and synergistically inhibited colony formation by PDAC cells and suppessed the growth of MiaPaCa-2 cells xenografted into the flank of nude mice. The results provide rationale for considering a combination(s) of FDA-approved SFK (dasatinib) and MEK (e.g. trametinib) inhibitors in prospective clinical trials for the treatment of PDAC." Read more at the source #DrGPCR #GPCR #IndustryNews

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  • Dr. GPCR Summit 2022 is coming!

    The 3rd edition of the Dr. GPCR Summit is between October 10th to the 16th! 💡Trainees are invited to participate by presenting a trainee talk, a poster, or a pre-recorded talk Become a site member for FREE and submit your info! ➡️ https://www.ecosystem.drgpcr.com/dr-gpcr-summit-2022 #gpcr #drgpcr

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    🔎 Are you a trainee? Would you like to develop your presentation skills? Give a talk or present a poster at the Dr. GPCR Summit 2022. Mark your calendar for October 10th and 16th. Become a site member for FREE and submit your abstract today! ➡️ https://www.ecosystem.drgpcr.com/ #gpcr #drgpcr

  • Dr. Rosie Dawaliby Podcast!

    We're very excited to announce the next episode of the Dr. GPCR podcast! 🥁 Drum rolls, please! Our guest is the wonderful Dr. Rosie Dawaliby! Watch the full video with a Dr. GPCR Ecosystem paid membership ➡️ https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/ep-84-with-rosie-dawaliby #gpcr #drgpcr

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    🌟 We're so excited about our upcoming Dr. GPCR Summit 2022. This is a great opportunity for us to come together and talk GPCRs. Do you want to be part of it? Our Summit is FREE for all Ecosystem site members, which is also free! Join us now ➡️ https://www.ecosystem.drgpcr.com/dr-gpcr-summit-2022 #gpcr #drgpcr

  • Addex Raises $10 Million In Equity Financing

    December 2021 "Geneva, Switzerland, December 17, 2021 – Addex Therapeutics Ltd (SIX: ADXN and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, today announced that it has entered into a definitive agreement with Armistice Capital LLC, a healthcare-focused institutional investor, pursuant to which the Company agreed to sell 3,752,202 shares in the form of 625,367 American Depositary Shares (“ADSs”) at a gross purchase price of $6.50 per ADS, which is equivalent to CHF 1.00 per share. Each ADS represents six shares. Additionally, Addex has agreed to issue to Armistice Capital unregistered warrants to purchase up to 9,230,772 shares in the form of 1,538,462 ADSs (the “Unregistered Warrants”), as well as unregistered pre-funded warrants to purchase up to 5,478,570 shares in the form of 913,095 ADSs (the “Unregistered Pre-Funded Warrants” and together with the Unregistered Warrants, the “Warrants”) in a concurrent private placement. The Unregistered Warrants have an exercise price of $6.50 per ADS, will become exercisable in 60 days after their date of issuance and will expire six years from their date of issuance. The Unregistered Pre-Funded Warrants have been funded to the amount of $6.49 with $0.01 payable on exercise." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Learn about Dr. GPCR Ecosystem!

    💻Did you know that Dr. GPCR is much more than a podcast? Come check out the brand new Dr. GPCR Ecosystem and explore its benefits! We have #GPCR News, Learning Center, Events, and more to discover! Learn More HERE ➡️ https://www.ecosystem.drgpcr.com/learning-center #gpcr #drgpcr

  • Carola Weiss joins InterAx Biotech AG as VP Business Development

    February 2022 "Switzerland Today, InterAx Biotech is pleased to announce that Carola Weiss has joined the company as VP Business Development. Carola Weiss is a Senior Executive with more than 20 years of international experience in the biopharmaceutical industry. Carola Weiss’ professional career brings deep expertise in business development, marketing & sales, licensing, alliance management, and strategic partnering. Her expertise guided numerous global negotiations, conclusions of partnership agreements, and fostered growth for her employers." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Addex Therapeutics CEO Tim Dyer: There is a $4-bil market opportunity in dyskinesia

    January 2022 "Watch our CEO Tim Dyer on AlphaStreet. In his interview, Mr. Dyer provides an overview of our #allostericmodulator pipeline and the potential $4 billion market for our lead compound #dipraglurant in #PDLID (#Parkinsonsdisease levodopa-induced #dyskinesia)." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Exscientia and Sanofi Establish Strategic Research Collaboration to Develop AI-driven Pipeline ...

    January 2022 Exscientia and Sanofi Establish Strategic Research Collaboration to Develop AI-driven Pipeline of Precision-Engineered Medicines "Collaborative efforts aim to accelerate drug discovery and improve clinical success Agreement to utilize Exscientia’s AI-based capabilities and personalised medicine platform from target identification through patient selection Research will be focused on up to 15 novel small molecule candidates across oncology and immunology Exscientia will receive an upfront cash payment of $100 million with the potential of $5.2 billion in total milestones plus tiered royalties PARIS & OXFORD, England & BOSTON--Sanofi and Exscientia announced today a groundbreaking research collaboration and license agreement to develop up to 15 novel small molecule candidates across oncology and immunology, leveraging Exscientia’s end-to-end AI-driven platform utilizing actual patient samples. The companies have been working together since 2016 and in 2019, Sanofi in-licensed Exscientia’s novel bispecific small molecule candidate capable of targeting two distinct targets in inflammation and immunology." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Trevena Announces Advancement of TRV045 Into Clinical Development for Diabetic Neuropathic Pain

    December 2021 "3-part randomized, double-blind, placebo-controlled Phase 1 study will evaluate TRV045 safety, tolerability, and PK in healthy volunteers Enrollment expected to start in early Q1 2022 CHESTERBROOK, Pa., Dec. 13, 2021 - Trevena, Inc. (Nasdaq: TRVN), a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with central nervous system (CNS) disorders, today announced it is advancing TRV045 into clinical development, following receipt of a notification from the U.S. Food and Drug Administration (FDA) that the study may proceed. TRV045 is the Company’s novel S1P1 receptor modulator being developed as a potential treatment for diabetic neuropathic pain (DNP). In addition, through a collaboration with the National Institutes of Health, the Company is also exploring TRV045 as a potential treatment for epilepsy." Read more at the source #DrGPCR #GPCR #IndustryNews

  • Neurocrine Biosciences Announces Positive Phase 3 Data for KINECT-HD Study Evaluating Valbenazine...

    December 2021 Neurocrine Biosciences Announces Positive Phase 3 Data for KINECT-HD Study Evaluating Valbenazine for Chorea Associated with Huntington Disease "Highly Statistically Significant Reduction in Chorea Movements (p < 0.0001) as Measured by the Unified Huntington's Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) Score- Placebo-Adjusted Mean Reduction in TMC Score of 3.2 Units in Valbenazine-Treated Patients- Company Plans to Submit Supplemental New Drug Application to U.S. Food and Drug Administration in 2022 SAN DIEGO, Dec. 7, 2021 /PRNewswire/ -- Neurocrine Biosciences (Nasdaq: NBIX) today announced positive top-line data from its Phase 3 KINECT-HD study evaluating the efficacy, safety and tolerability of valbenazine, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor being investigated as a once-daily treatment in adults with chorea associated with Huntington disease (HD). The study met the primary endpoint of reduction in severity of chorea, the cardinal motor feature in Huntington disease, as measured by change in the Unified Huntington's Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score from baseline to the average score at weeks 10 and 12. " Read more at the source #DrGPCR #GPCR #IndustryNews

  • Oxford Professor Of Chemistry And Founder Of Therapeutic Company Wins Two International Awards

    December 2021 "Dame Carol Robinson DBE, FRS, FRSC, FMedSci, Oxford University’s first female Professor of Chemistry, former president of the Royal Society of Chemistry and Founder of (and ongoing consultant to) OMass Therapeutics, which is based at Oxford Science Park, has been awarded the 2022 Louis-Jeantet Prize for Medicine. This is a highly prestigious international award – exemplified by the fact that other winners this year are the co-founders of BioNTech for their invention of the (Pfizer) Covid vaccine." Read more at the source #DrGPCR #GPCR #IndustryNews

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