September 2022 "For decades, glioblastoma multiforme (GBM), a type of the most lethal brain tumor, has Recently, many novel discoveries have underlined the regulatory roles of neurotransmitters in the microenvironment ligands acting on neurotransmitter receptors have shown great potential for inhibiting GBM growth and development potential targeted drugs used for GBM treatment." Read more at the source #DrGPCR #GPCR #IndustryNews

Read more at the source #DrGPCR #GPCR #IndustryNews

Cryo-electron microscopy studies revealed a drastic conformational change upon activation and a unique find that the inactive GP first interacts with TM3, which further leads to the TMD rearrangement and deeper This mechanism provides fresh insights into the mechanistic details of class C GPCRs activation expected to be useful for designing selective agonists and antagonists." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "The diamondback moth (Plutella xylostella) is one of the most destructive lepidopteran The injection of double-stranded RNA in an RNA interference assay indicated that PxOctβ3 regulates development This study demonstrated the pharmacological properties and functions of PxOctβ3 in P. xylostella, thus , providing a theoretical basis for the design of pesticides that target octopamine receptors." Read more at the source #DrGPCR #GPCR #IndustryNews

NETs were also detected in thrombotic lesions in several disease backgrounds, pointing towards a role The negatively charged DNA within NETs provides a procoagulant surface, and in particular NET-derived proteins may directly activate platelets. to influence the course of inflammatory diseases. Read more at the source #DrGPCR #GPCR #IndustryNews

Read more at the source #DrGPCR #GPCR #IndustryNews

Through (un)biased molecular dynamics simulations and mutagenesis experiments, we show that TM2 rearrangement findings fill a gap in the understanding of CB1 allosteric regulation and could guide the rational design Read more at the source #DrGPCR #GPCR #IndustryNews

For class B GPCRs, previous molecular dynamics (MD) simulation studies have shown PI(4,5)P2 interacting with the Glucagon receptor (GCGR), which constitutes an important target for diabetes and obesity therapeutics We demonstrate how tail composition plays a role in modulating the binding of PI(4,5)P2 lipids to GCGR This suggests differences in the regulatory function of PI(4,5)P2 between class A and class B GPCRs." Read more at the source #DrGPCR #GPCR #IndustryNews

Gγ1, Gγc, or Gγ11 in Gγ1-deficient mice and analyzed their properties. rod cells and restoration of Gαt1 expression, which is greatly reduced in Gγ1-deficient rods. In all dark-adapted transgenic lines, Gαt1 was targeted to the outer segments, reversing its diffuse localization found in Gγ1-deficient rods. Read more at the source #DrGPCR #GPCR #IndustryNews

macrophages and monocytes, and play a critical role in neuroinflammatory conditions such as Alzheimer's disease In this work we present the study of the CX3CR1 receptor employing extensive atomistic Molecular Dynamics We analyzed the receptor conformational changes and described interactions within its key regions and the bounded ligands to identify their notable differences. Read more at the source #DrGPCR #GPCR #IndustryNews

study, we compared GPR39 expression between colon cancers and tumor-adjacent tissues by retrieving TCGA data and detected the expression of GPR39 in colon cancers with qPCR and immunohistochemistry. of several other biomarkers including PPARG, EPCAM, and PD-L1 was investigated by re-analyzing TCGA data Read more at the source #DrGPCR #GPCR #IndustryNews

Using different optical biosensors to measure the activation of PTH1R and its downstream signaling, we describe here that RAMP2 acts as a specific allosteric modulator of PTH1R, shifting PTH1R to a unique Moreover, RAMP2 modulates PTH1R downstream signaling in an agonist-dependent manner, most notably increasing a new venue for highly specific modulation of GPCR function and advanced drug design." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor In this article, we describe a 2.2 Å resolution room temperature crystal structure of the human S1P5 the receptor subtype selectivity and provides a template for structure-based drug design. Read more at the source #DrGPCR #GPCR #IndustryNews

and a middle sized flexible molecule "A GA-guided multidimensional virtual-system coupled molecular dynamics Then sampling was conducted from conformations where bosentan was distant from the binding site in the The deepest basin in the resultant free-energy landscape was assigned to native-like complex conformation During this sliding, bosentan passes the gate of the binding pocket from outside to inside of the pocket Read more at the source #DrGPCR #GPCR #IndustryNews

The 5HT2C serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms These 5HT2C isoforms display differences in constitutive activity, agonist/inverse agonist potencies, 5HT2C-transducer-coupled structures of three representative isoforms (INI, VGV, and VSV) with the selective drug unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which differentially Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Systemic sclerosis (SSc) is a systemic autoimmune disease with the key features of inflammation dysregulated in SSc. in more detail. Extracellular vesicles are another novel player to possess disease processes. Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Yeast use the G-protein–coupled receptor signaling pathway to detect and track the mating the regulator of G-protein signaling (RGS) Sst2 which induces Gα GTPase activity and inactivation of downstream We also found overexpression of unphosphorylatable RGS exacerbates cytokinetic defects, whereas they These data lead us to a model where Kel1 promotes completion of cytokinesis before pheromone-induced Read more at the source #DrGPCR #GPCR #IndustryNews

patient outcomes "Triple-negative breast cancer (TNBC) is a particularly aggressive and heterogeneous disease breast cancer, while a new estrogen receptor, namely G protein-coupled estrogen receptor (GPER), is demonstrated survival (DMFS) ( P  = 0.014) was found by Kaplan–Meier analysis in patients with high GPER expression Furthermore, univariate analysis confirmed that GPER was a significant prognostic factor for DMFS in Read more at the source #DrGPCR #GPCR #IndustryNews

Previous findings suggest that parallel pathways independently relay innate threat signals from different The identification of unified innate threat pathways may provide insights into developing therapeutic candidates for innate fear-related disorders." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Experimental studies proposed a direct effect of follicle-stimulating hormone (FSH) on Read more at the source #DrGPCR #GPCR #IndustryNews

cancer therapies focuses on processes such as angiogenesis, cell signaling, stemness, metastasis, and drug Different strategies, such as antibodies, small chemicals, hormones, cytokines, and, recently, gene editing Few therapeutic agents have shown benefits when administered alone, but a few more have demonstrated , increasing evidence of its antitumoral properties in more than a dozen different types of cancer. Read more at the source #DrGPCR #GPCR #IndustryNews

MRP extrusion capacity was determined by intracellular 5 (6)-Carboxyfluorescein diacetate (CFDA) accumulation Cell cycle and apoptosis were determined by flow cytometry. Downregulation of the A2B receptor decreases MRP3 expression and chemosensibilizes GSCs treated with These data suggest that hypoxia-dependent activation of A2B adenosine receptor promotes survival of GSCs Read more at the source #DrGPCR #GPCR #IndustryNews

inflammation in mice following mild traumatic brain injury "Traumatic brain injury (TBI) is a leading cause of disability peptide, acts at the G protein coupled MAS1 receptors (MASR) to inhibit inflammatory mediators and decrease Few studies have identified whether Ang-(1-7) decreases cognitive impairment following closed TBI. Read more at the source #DrGPCR #GPCR #IndustryNews

In this study, we found that [Ca2+]i elevation and voltage-dependent current generated by MRGPRB2 activation The increases in [Ca2+]i and voltage-dependent current caused by MRGPRB2 activation were blocked by U73122 The voltage-dependent current induced by MRGPRB2 was inhibited by calcium-activated chlorine channel (CACCS) blockers, DIDS, or NPPB. Read more at the source #DrGPCR #GPCR #IndustryNews

N-terminal fragment 1 to 36 "The parathyroid hormone (PTH)-related protein (PTHrP) is indispensable for the development 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 Furthermore, we show that the molecular basis for biased signaling differences between PTHrP1-36 and Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "G-protein-coupled receptors (GPCRs) are involved in a wide array of physiological and disease Both PAR4 and PAR2 are able to drive the association of methyltransferase EZH2 with β-catenin, culminating Indeed, EZH2 is found to be directly correlated with high PAR4-driven tumors, and is abundantly expressed A truncated form of β-catenin, ∆N133β-catenin, devoid of lysine, as well as serine/threonine residues Read more at the source #DrGPCR #GPCR #IndustryNews

Heterodimerization decreased TrkB autophosphorylation, preventing its activation with agonist 7,8-DHF of TrkB phosphorylation without restoring the TrkB response to its agonist 7,8-DHF in vitro. HT2A may shift in certain brain regions during postnatal development. development and under pathophysiological conditions." Read more at the source #DrGPCR #GPCR #IndustryNews

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. Surprisingly, our results also demonstrate that exposure to SFK inhibitors, including dasatinib or knockdown Read more at the source #DrGPCR #GPCR #IndustryNews