Search Results

"Protecting neurons from death during oxidative and neuroexcitotoxic stress is key for preventing cognitive dysfunction. We uncovered a novel neuroprotective mechanism involving interaction between neurotrophic factor-α1 (NF-α1/carboxypeptidase E, CPE) and human 5-HTR1E, a G protein-coupled serotonin receptor with no previously known neurological function. Co-immunoprecipitation and pull-down assays confirmed interaction between NFα1/CPE and 5-HTR1E and 125I NF-α1/CPE-binding studies demonstrated saturable, high-affinity binding to 5-HTR1E in stably transfected HEK293 cells (Kd = 13.82 nM). Treatment of 5-HTR1E stable cells with NF-α1/CPE increased pERK 1/2 and pCREB levels which prevented a decrease in pro-survival protein, BCL2, during H2O2-induced oxidative stress. Cell survival assay in β-arrestin Knockout HEK293 cells showed that the NF-α1/CPE-5-HTR1E-mediated protection against oxidative stress was β-arrestin-dependent. Molecular dynamics studies revealed that NF-α1/CPE interacts with 5-HTR1E via 3 salt bridges, stabilized by several hydrogen bonds, independent of the serotonin pocket. Furthermore, after phosphorylating the C-terminal tail and intracellular loop 3 (ICL3) of NF-α1/CPE-5-HTR1E, it recruited β-arrestin1 by forming numerous salt bridges and hydrogen bonds to ICL2 and ICL3, leading to activation of β-arrestin1. Immunofluorescence studies showed 5-HTR1E and NF-α1/CPE are highly expressed and co-localized on cell surface of human hippocampal neurons. Importantly, knock-down of 5-HTR1E in human primary neurons diminished the NF-α1/CPE-mediated protection of these neurons against oxidative stress and glutamate neurotoxicity-induced cell death. Thus, NF-α1/CPE uniquely interacts with serotonin receptor 5-HTR1E to activate the β-arrestin/ERK/CREB/BCL2 pathway to mediate stress-induced neuroprotection." Read full article

Two compounds can show identical affinities on paper, but their biological outcomes can differ dramatically s Corner   ______ #DrugDiscovery #Pharmacology #DrugKinetics #PipelineEfficiency #PharmaInnovation #GPCR

GPCRs represent major drug targets, as indicated by the fact that about 40% of all drugs currently used in clinical practice mediate their therapeutic effects by acting on GPCRs. Like many other organs, various GPCRs play a role in regulating liver function. It is predicted that more than 50 GPCRs are expressed in the liver. However, our knowledge of how GPCRs regulate liver metabolism and fibrosis in the different cell types

accelerate and improve the prediction of first-in-class small molecule agonists for a challenging orphan GPCR #ai #biotech #systemsbiology #drugdiscovery #gpcr #deeptech #orphandrugs #pharma #partnerships #AI4drugdiscovery " Read more at the source #DrGPCR #GPCR #IndustryNews

protein-coupled receptor expression: Implications for metabolic regulation G protein-coupled receptors (GPCRs their secretion of insulin, and islet function can be modified by ligands acting at the large number of GPCRs is altered under pathophysiological conditions and, in this review, we have compared expression of GPCR We have also considered the likely outcomes on islet function that the altered GPCR expression status confers and the possible impact that adipokines, secreted from expanded fat depots, could have at those GPCRs

Kenakin walks through this as a living system , showing how GPCRs exist in multiple conformations and Watch our new trailers for a preview of expert-led GPCR training designed for scientists and drug hunters GPCR members save  50%+  (check your Weekly News code).

Read more at the source #DrGPCR #GPCR #IndustryNews

chemistry decisions Why Live-cell High-Content Screening Matters for CB2 Ligand Profiling CB2 is a GPCR For GPCR programs—where trafficking, receptor reserve, and internalization are common confounders—access For researchers working in cannabinoid pharmacology, inflammation, or GPCR-mediated analgesia, these

Yet, any pharmacologist who’s pushed beyond textbook theory knows: biology rarely plays fair. Schild analysis remains the simplest, most revealing conversation we can have with biology. GPCR innovation is accelerating—those who act now will define tomorrow’s breakthroughs.

In this sense, G protein-coupled receptors (GPCRs) may be a good option to try to prolong our life while In this way, we present the analysis of a series of GPCRs whose activity has been shown to affect the Our compilation of data revealed that the mechanisms most involved in the role of GPCRs in lifespan are possibility of using agonist or antagonist drugs, depending on the beneficial or harmful effects of each GPCR

#artificialintelligence #drugdesign #drugdiscovery" Read more at the source #DrGPCR #GPCR #IndustryNews

allosteric binding site (IABS) has recently been identified at several G protein-coupled receptors (GPCRs previous phase III clinical candidate for the treatment of Crohn's disease, we developed a chemical biology To chemically induce CCR9 degradation, we then developed the first PROTAC targeting the IABS of GPCRs our CCR9-PROTAC is able to reduce CCR9 levels, thereby offering an unprecedented approach to modulate GPCR

vitro and in vivo data suggest that GHSR1a heterodimerises with multiple G protein-coupled receptors (GPCRs This review discusses the signalling mechanisms of GHSR1a alone and in combination with other GPCRs, and explores the physiological consequences of GHSR1a coupling with other GPCRs.

#technology #lifescience #immunology #antibodies #medicine #cancer #innovation #gpcr #synabs #monoclonalantibodies #drugdiscovery #biotechnology #research #ionchannels #biologics #biotech #pharma #pharmaindustry #pharmaceuticals #oncology #healthcare #drugdevelopment" Read more at the source #DrGPCR #GPCR #IndustryNews

#ForbesUnder30 #ArcoScreen #sciences #EPFL" Read more at the source #DrGPCR #GPCR #IndustryNews

GPCR Podcast, Dr. Maria Majellaro makes it clear that Celtarys isn’t just a ligand provider. GPCR so powerful. “We don’t just deliver compounds, we solve assay problems.” — Dr. “We want to illuminate biology. That’s the mission. ” — Dr. . _______________ Keyword Cloud:   GPCR data platform , fluorescent ligands , assay development , GPCR GPCR ecosystem , GPCR webinar series

Read more at the source #DrGPCR #GPCR #IndustryNews

structural positions in class A G protein-coupled receptors expressed in tumors G protein-coupled receptors (GPCRs Because there are many more GPCRs than effectors, mutations in different receptors could perturb signaling may not be enriched within a single gene but rather that cognate mutations with similar effects on GPCR To test this possibility, we systematically aggregated somatic cancer mutations across class A GPCRs The possibility that multiple different GPCRs could moonlight as drivers or enablers of a given cancer

mechanosensation-dependent behavior in C. elegans via a trans function Latrophilins are highly conserved Adhesion GPCRs

forward for more 🎊 #team #grateful #biotech #work #birthdaycelebration" Read more at the source #DrGPCR #GPCR

We also identified two Gs-coupled GPCRs that are endogenously expressed by SKM at relatively high levels

of the Inflammatory Cytokine IL-6 and Is Dependent on NF-κB Signaling G protein-coupled receptors (GPCRs Members of the Mas-related G protein coupled receptors (MRGPRs), a subfamily of GPCRs, are largely expressed

#DrugDiscovery #MassSpec #Award #massspectrometry" Read more at the source #DrGPCR #GPCR #IndustryNews

receptor-ligand complexes: Impact of ligand type and receptor activation state G protein-coupled receptors (GPCR Their abundance and role in nearly all physiological systems make GPCR the largest protein family targeted provided broadly generalizable performance expectations for docking into experimentally-characterized GPCR Simulations were performed using 37 experimental structures of 11 Class A GPCR crystallized in multiple Therefore, docking performance against GPCR targets can be estimated in advance based on docking target

Ho, ho, ho, GPCR elves! GPCR ecosystem! Best, Yamina & the Dr. and TPD Structural Biology Platforms GPCR Events, Meetings, and Webinars December 10 - 12, 2024 | Jobs GPCR Molecular Pharmacologist Scientist - Biology Scientist I Cell Biology - Tectonic Therapeutic Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist

bioactive phospholipids implicated in a wide range of cellular activities that regulate a diverse array of biological

GPCR Podcast, she shares how her background in medicinal chemistry paved the way to co-founding Celtarys , a company now shaping the future of GPCR assay tools. Over time, she developed a fascination with how molecules influence biology and how that chemistry could drug discovery , GPCR research community , medicinal chemistry , Dr. GPCR ecosystem , GPCR online course , GPCR scientist network

a startup delivering tools for GPCR drug discovery. specialization in pharmaceutical chemistry, a degree that allowed her to see the full picture from synthesis to biology GPCR on the company page . _______________ Keyword Cloud:   GPCR scientist network , career development , fluorescent ligands , GPCR training program , Dr. GPCR ecosystem , GPCR podcast

Electron cryo-microscopy (cryo-EM) is a powerful technique for the structural characterization of biological cryo-EM has enabled insights into important drug target families such as G protein-coupled receptors (GPCRs Structural characterization of biologics, such as vaccines, viral vectors, and gene therapy agents, has

pharmaceutical chemist, Alessandro never imagined himself working at the cutting edge of computational GPCR began their mission: to computationally study olfactory GPCRs , a massively under-characterized group With hundreds of subtypes and limited ligand data, olfactory GPCRs represent a high-risk, high-reward —Alessandro Nicoli Want to explore computational GPCR science yourself? Explore the   GPCR University  or enroll in Terry's Corner for GPCR Courses led by Dr.