August 2022 "Alzheimer's disease (AD) is the most common dementia in the elderly and its increasing prevalence Despite a better understanding of the disease, the current mainstay of treatment cannot modify pathogenesis or effectively address the associated cognitive and memory deficits. discovery success and enhance the therapeutic response." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Cardiovascular diseases (CVDs) represent the leading cause of death globally. Despite major advances in the field of pharmacological CVD treatments, particularly in the field of heart Additionally, the GRK2 interactome includes numerous proteins which interact with differential domains These data support the premise that GRK2 should be at the forefront of a novel investigative drug search Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 TAS2R supports odontoblastic differentiation of human dental pulp stem cells in the inflammatory microenvironment " Background: Inflammatory microenvironment promotes odontoblastic differentiation in human dental pulp stem cells (hDPSCs), but the regulatory mechanisms remain unclear. In this study, we aimed to explore the role of TAS2R in odontoblastic differentiation of hDPSCs in the Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "G-protein-coupled receptors (GPCR) are present at the cell surface in different conformational We used TIRF microscopy and a statistical method to track and classify the motion of different receptor We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric These forms were stabilized differently by distinct ligands. our quantitative analysis revealed agonist-like properties of gp120s. " Read more at the source #DrGPCR

SST5 homo- and hetero-dimer formation "The process of GPCR dimerization can have profound effects on Using the PLA approach combined with epitope tagging, we detected homo-dimers of human SST2 in GH3, A7 SST2 and SST5 can also form endogenous hetero-dimers in these cells. In conclusion, we demonstrated that in GH3 cells SST2 and SST5 can form both homo- and hetero-dimers Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Background Cancer driver genes are usually ranked by mutation frequency, which does not necessarily reflect their driver strength. We hypothesize that driver strength is higher for genes preferentially mutated in patients with few driver Methods We propose formulas for the Driver Strength Index (DSI) and the Normalized Driver Strength We validate them using TCGA PanCanAtlas datasets, established driver prediction algorithms and custom

from inactive conformation using molecular dynamic simulations "The δ-opioid receptor (DOR) is a critical In this study, a DOR agonist ADL5859 was docked to the inactive DOR and multiple microsecond molecular dynamic (MD) simulations were conducted to probe the activation mechanism. These insights will facilitate further development of therapeutic agents targeting the DOR.Communicated Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Interacting binding insights and conformational consequences of the differential activity , Parkinson’s disease, and Alzheimer’s disease. In particular, CBD is able to modulate different receptors in the endocannabinoid system, some of which The details of this dual contrasting functional feature of CBD, that is, displaying antagonistic and Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Parkinson’s disease (PD) as a progressive neurodegenerative disorder arises from multiple Additionally, we detect a shortening of PC in PINK1 -deficient human cellular and mouse models of familial Thus, increased SHH activity due to ciliary dysfunction may be required for the development of pathoetiological phenotypes observed in sPD like mitochondrial dysfunction. Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 β2-Adrenergic Receptor Expression and Intracellular Signaling in B Cells Are Highly Dynamic during Collagen-Induced Arthritis "The sympathetic nervous system (SNS) has either a pro-inflammatory or anti-inflammatory effect, depending on the stage of arthritis. CIA without a change in receptor density. Read more at the source #DrGPCR #GPCR #IndustryNews

A central question of GPCR drug discovery is to understand what determines the agonism or antagonism that mediate their action and that among a large dataset of different ligands, the functionally important discovery process. This approach can be readily applied to any drug target." Read more at the source #DrGPCR #GPCR #IndustryNews

The mechanism by which the MOR distinguishes between the two is unclear. are used here to determine the different interactions of these two ligands with MOR: morphine adjusted its pose by continuously flipping deeper into the pocket, whereas naloxone failed to penetrate deeper This finding reveals a dynamic mechanism for the response of MOR to different ligands and provides a Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism Such effects are mediated by the suppression of gut IEL effector functions linked to the dampening of proximal T cell receptor signaling in a protein-kinase-A-dependent manner. These data reposition key roles of the L cell-gut IEL GLP-1R axis, revealing mechanisms linking GLP-1R Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Ginsenoside Rg5 allosterically interacts with P2RY12 and ameliorates deep venous thrombosis by counteracting neutrophil NETosis and inflammatory response "Deep venous thrombosis (DVT) highly occurs DVT formation is a time-dependent inflammatory process in which NETosis plays an important role. However, whether ginsenoside Rg5 from species of Panax genus could alleviate DVT and its underlying mechanism Read more at the source #DrGPCR #GPCR #IndustryNews

December 2021 "3-part randomized, double-blind, placebo-controlled Phase 1 study will evaluate TRV045 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). Read more at the source #DrGPCR #GPCR #IndustryNews

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 Food and Drug Administration in 2022 SAN DIEGO, Dec. 7, 2021 /PRNewswire/ -- Neurocrine Biosciences ( treatment in adults with chorea associated with Huntington disease (HD). " Read more at the source #DrGPCR #GPCR #IndustryNews

the vast potential for GPCR-targeting drugs in treating a range of health conditions, from cancer and genetic disorders to inflammation and metabolic imbalances. new GPCR targets that’ll fuel the development of potential drug candidates. team-ups in GPCR-based drug discovery have clocked in at $1 billion—with Genentech—and, just last November Read more at the source #DrGPCR #GPCR #IndustryNews

April 2022 Ono Enters into Collaboration Agreement with Domain Therapeutics and Université de Montréal for GPCR-Targeted Drug Discovery " Apr.19.2022 　 Ono Pharmaceutical Co., Ltd. (Strasbourg, France; CEO: Pascal Neuville ; “Domain”) and Université de Montréal (Québec, Canada; “UdM ”), to discover novel small molecules targeting G-Protein Coupled Receptors (GPCRs) in a metabolic disease Read more at the source #DrGPCR #GPCR #IndustryNews

July 2022 " Orion Biotechnology and Peptilogics are pursuing AI-driven drug discovery to explore new #ai #drugdiscovery #gpcr" Read more at the source #DrGPCR #GPCR #IndustryNews

December 2021 "Drug development is rarely trivial. The sheer complexity of the cell and the astonishing diversity of diseases are just two reasons why researchers typically require years to uncover the mechanisms of disease before they can even dare to contemplate Drugs that do make it to clinical trials have major hurdles to clear—not the least of which is safety must be deemed tolerable before investigators can assess drug potency.

However, in drug discovery projects, perfection can’t be attained soon enough. A project to develop a perfect drug, or a drug that is as safe and effective as possible, may never begin If only Voltaire were here today to see how drug discovery is being accelerated by new technologies. Several new technologies that are being used to accelerate drug discovery are highlighted in this article Read more at the source #DrGPCR #GPCR #IndustryNews

S1R has been implicated in many neurological disorders such as anxiety, schizophrenia, and depression -2,4-dione nucleus. 6c resulting in 100% displacement and a Ki of 95.5 nM. Glu172 with variable degrees of π-stacking interaction with Tyr103. Read more at the source #DrGPCR #GPCR #IndustryNews

June 2022 "Ottawa, Canada, May 10, 2022 — Orion Biotechnology Canada Ltd, a drug discovery and development Dr. Oliver Hartley , Orion’s Vice-President Drug Discovery, will present Orion’s novel technology for targeting His presentations will describe Orion’s drug discovery platform, one of the fastest drug discovery solutions Dr.

GPCRs are divided into six classes based on amino acid sequence similarities, but only four of the classes GPCRs continue to be regarded as one of the most tractable classes of drug targets and are targeted by 30%–40% of current drugs (Hauser et al., 2017), with annual sales of GPCR-targeting drugs in 2018 accounting Despite this high number of GPCR targeted drugs, only a small portion (∼110) of the human GPCRome (consisting Read more at the source #DrGPCR #GPCR #IndustryNews

of Biochemistry and Molecular Medicine of the Faculty of Medicine of the Université de Montréal , is appointed Knight of the Ordre national du Québec. This honorary decoration, bestowed today by the government of Quebec, is the highest honour in Quebec It has been awarded annually since 1985 to distinguished individuals who have strived, in an exceptional Read more at the source #DrGPCR #GPCR #IndustryNews

April is the month of DNA Day, a special day commemorating the discovery of the DNA double helix structure United States. https://www.genome.gov/ Dixon, R. A., Kobilka, B. K., Strader, D. J., Benovic, J. ., Dohlman, H. G., Frielle, T., Bolanowski, M. A., Bennett, C. D., Rands, E., Diehl, R. D. (1986). B., Panova, O., Hilger, D., Casiraghi, M., He, F., Maul, L., Gmeiner, P., Kobilka, B.

May 2022 "Published: May 10, 2022 To accelerate clinical development of its best-in-class and first-in-class immuno-oncology programs STRASBOURG, France & MONTREAL- Domain Therapeutics , a biopharmaceutical company specializing in the research and development of innovative drugs targeting G Protein-Coupled Read more at the source #DrGPCR #GPCR #IndustryNews

April 2022 "By Sophie Bradley | Apr 12, 2022 Summary Sophie Bradley, Translational Sciences Associate Director University characterizing the role of the muscarinic M1 receptor in cognitive and neurodegenerative disorders Read more at the source #DrGPCR #GPCR #IndustryNews