September 2022 Dynamics of tumor-associated macrophages in a quantitative systems pharmacology model antibody atezolizumab and nab-paclitaxel has shown clinical activity in advanced TNBC with PD-L1-positive tumor-infiltrating As tumor-associated macrophages (TAMs) serve as major contributors to the immuno-suppressive tumor microenvironment We show that through proper calibration, the model captures the macrophage heterogeneity in the tumor

and inflammation, all of which are influenced by the cellular and molecular microenvironment of the tumor techniques, have been tested to reduce the malignancy and generate a harmful microenvironment for the tumor therapeutic benefits of the β-adrenergic receptor antagonist, propranolol, were described in benign tumors

October 2022 "Pepducins are small-lipidated peptides designed from the intracellular loops of G protein-coupled receptors (GPCRs) that act in an allosteric manner to modulate the activity of GPCRs. Over the past 2 decades, pepducins have progressed initially from pharmacologic tools used to manipulate GPCR activity in an orthosteric site-independent manner to compounds with therapeutic potential that have even been used safely in phase 1 and 2 clinical trials in human subjects. The effect of pepducins at their cognate receptors has been shown to vary between antagonist, partial agonist, and biased agonist outcomes in various primary and clonal cell systems, with even small changes in amino acid sequence altering these properties and their receptor selectivity. To date, pepducins designed from numerous GPCRs have been studied for their impact on pathologic conditions, including cardiovascular diseases such as thrombosis, myocardial infarction, and atherosclerosis. This review will focus in particular on pepducins designed from protease-activated receptors, C-X-C motif chemokine receptors, formyl peptide receptors, and the β2-adrenergic receptor. We will discuss the historic context of pepducin development for each receptor, as well as the structural, signaling, pathophysiologic consequences, and therapeutic potential for each pepducin class." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Glucagon receptor-mediated regulation of gluconeogenic gene transcription is endocytosis-dependent We tested if this is true for the glucagon receptor (GCGR), which mediates physiological regulation of

Here, using colorectal cancer (CRC) as a model, we explored the gene expression of a panel of GPCRs in tumor live-imaging modalities, and displayed high efficiency when used to label complex 3D cellular systems such as tumor A2BAR as a potential pharmacological tool in CRC, using selective antagonists, finding a reduction in tumor

October 2022 Coincident Regulation of PLCβ Signaling by Gq-Coupled and μOpioid Receptors Opposes Opioid- Mediated

August 2022 " Background and purpose: Vascular tone is regulated by the relative contractile state of vascular smooth muscle cells (VSMCs). Several integrins directly modulate VSMC contraction by regulating calcium influx through L-type voltage-gated Ca2+ channels (VGCCs). Genetic variants in ITGA9, which encodes the α9 subunit of integrin α9β1, and SVEP1, a ligand for integrin α9β1, associate with elevated blood pressure; however, neither SVEP1 nor integrin α9β1 has reported roles in vasoregulation. We determined whether SVEP1 and integrin α9β1 can regulate VSMC contraction." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "G protein-coupled receptor (GPCR) kinases (GRKs) and arrestins mediate GPCR desensitization The spatial pattern of GPCR phosphorylation is predicted to trigger these discrete GRK and arrestin-mediated We demonstrate by pharmacologic inhibition of GRK2/3-mediated phosphorylation of the chemokine receptor conclusion, this study provides evidence that distal C-tail phosphorylation sites specify GRK-βarrestin-mediated

25-81) and GPR15L(71-81) are used as pharmacological tool compounds to delineate the GPR15 receptor-mediated

August 2022 Dopamine D 1 receptor-mediated β-arrestin signaling: Insight from pharmacology, biology, We now summarize important pharmacological, molecular, and cellular studies relevant to D1-mediated β-arrestin-related many results emerged from behavioral and physiological studies implying that bias toward or against D1-mediated

G protein-coupled receptor kinase 2 is essential to enable vasoconstrictor-mediated arterial smooth muscle Vasoconstrictor-stimulated phosphorylation of the Akt substrates GSK3α and GSK3β was ablated following RNAi-mediated proliferation through its ability to promote efficient prolonged PI3K-Akt signalling, and thus relieve the GSK3-mediated

Constitutive, Basal, and β-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor of the human Mas-related G-protein coupled receptor D (MRGPRD) in the regulation of the inflammatory mediator Consequently, the dynamic range for IL-6 detection as an assay for β-alanine-mediated activation of MRGPRD Overall, the observation that MRGPRD mediates the release of IL-6 in an in vitro system, hints at a role as an inflammatory mediator and supports the notion that IL-6 can be used as a marker for MRGPRD activation

Sandra Berndt talk about new structural perspectives in GPCR-mediated Src family kinase activation.

This study demonstrated Gαq-G-protein coupled receptor (GPCR)-mediated [Ca2+]i signaling involvement cartilage-like matrix production, and it established hM3Dq as a powerful tool for elucidating the role of GPCR-mediated

The hepatitis B virus X protein (HBx) is involved in the process of hepatocellular carcinoma via the activation of various oncogenes. Our previous study indicated that ARBB1 (arrestin beta 1) promotes hepatocellular carcinogenesis (HCC). However, the role of ARRB1 in HBx-related HCC remains unclear. Herein, we identified that ARRB1 was upregulated by HBx in vivo and in vitro. Arrb1 deficiency suppressed HBx-induced hepatocellular carcinogenesis in several mouse models. Furthermore, knockdown of ARRB1 blocked HBx-induced macroautophagic/autophagic flux and disrupted the formation of autophagosomes. ARRB1 interacted with HBx, and the autophagic core protein MAP1LC3/LC3, a scaffolding protein, was essential for complete autophagy. Inhibition of autophagy by 3-methyladenine or interference of ATG5 or ATG7 attenuated HBx-induced cell cycle acceleration and the subsequent proliferative response via the induction of G1/S arrest. The absence of autophagy abolished the phosphorylation of CDK2 and the activity of the CDK2-CCNE1 complex. Our results demonstrate that ARRB1 plays a critical role in HBV-related HCC via modulating autophagy and the CDKN1B-CDK2-CCNE1-E2F1 axis and indicate that ARRB1 may be a potential therapeutic target for HCC. Abbreviations: ARRB1: arrestin beta 1; ACTB: actin beta; AMPK: adenosine monophosphate (AMP)-activated protein kinase; ATG5: autophagy related 5; ATG7: autophagy related 7; Baf A1: bafilomycin A1; CDK2: cyclin dependent kinase 2; CDKN1B/p27Kip1: cyclin dependent kinase inhibitor 1B; CQ: chloroquine; E2F1: E2F transcription factor 1; FBS: fetal bovine serum; GPCRs: G protein-coupled receptors; GST: glutathione S-transferase; HCC: hepatocellular carcinoma; HBV: hepatitis B virus; HBx: hepatitis B virus X protein; HMGB1: high mobility group box 1; HIF1A/HIF-1α: hypoxia inducible factor 1 subunit alpha; IHC: immunohistochemistry; JAK1: Janus kinase 1; LOX: lysyl oxidase; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MKI67: marker of proliferation Ki-67; MTOR: mechanistic target of rapamycin kinase; MAPK: mitogen-activated protein kinase; 3-MA: 3-methyladenine; NFKB/NF-κB: nuclear factor kappa B; PIK3CA: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PHHs: primary human hepatocytes; RB1: RB transcriptional corepressor 1; SQSTM1/p62: sequestosome 1; STAT: signal transducer and activator of transcription; TACR1/NK1R: tachykinin receptor 1. Read full article

(Gγ) prenylation under suboptimal conditions Exploiting frequent and specific expression of PRL3 in pediatric solid tumors for first-in-child use of PRL3-zumab humanized antibody Activation of PI3K/Akt pathway

in Adolescents with Classic CAH - Two Phase 3 Global Registrational Studies Currently Underway in Pediatric

August 2022 "The calcium-permeable cation channel TRPM3 can be activated by heat and the endogenous steroid pregnenolone sulfate. TRPM3's best understood function is its role as a peripheral noxious heat sensor in mice. However, the channel is expressed in various tissues and cell types including neurons as well as glial and epithelial cells. TRPM3 expression patterns differ between species and change during development. Furthermore, a plethora of TRPM3 variants that result from alternative splicing have been identified and the majority of these isoforms are yet to be characterized. Moreover, the mechanisms underlying regulation of TRPM3 are largely unexplored. In addition, a micro-RNA gene (miR-204) is located within the TRPM3 gene. This complexity makes it difficult to obtain a clear picture of TRPM3 characteristics. However, a clear picture is needed to unravel TRPM3's full potential as experimental tool, diagnostic marker and therapeutic target. Therefore, the newest data related to TRPM3 have to be discussed and to be put in context as soon as possible to be up-to-date and to accelerate the translation from bench to bedside. The aim of this review is to highlight recent results and developments with particular focus on findings from studies involving ocular tissues and cells or peripheral neurons of rodents and humans." Read more at the source #DrGPCR #GPCR #IndustryNews

while a new estrogen receptor, namely G protein-coupled estrogen receptor (GPER), is demonstrated to mediate the worse survival in patients with lymph node metastasis, TNM stage III as well as nuclear grade G3 tumors These results may supply new insights into GPER-mediated estrogen carcinogenesis in TNBC, thus providing

in the rat retrosplenial cortex Unveiling the therapeutic prospects of EGFR inhibition in rotenone-mediated FDA Accepts New Drug Applications and Grants Priority Review for Crinecerfont for Pediatric and Adult

Insights into MRP3 Transporter Function "Glioblastoma is the most common and aggressive primary brain tumor The chemoresistance of GSCs is mediated in part by adenosine signaling and ABC transporters, which extrude

GPCRs with receptor activity-modifying proteins Molecular mechanism of bitter taste receptor agonist-mediated Novel Urotensin II Receptor Modulators GPCRs in Oncology and Immunology G protein-coupled receptor-mediated signaling of immunomodulation in tumor progression Methods & Updates in GPCR Research GPCR Signaling

GPCRs in Neuroscience Role of G-Proteins and GPCR-Mediated Signalling in Neuropathophysiology. GPR4 in the pH-dependent migration of melanoma cells in the tumor microenvironment. Fusarium graminearum Ste3 G-Protein Coupled Receptor: A Mediator of Hyphal Chemotropism and Pathogenesis dosed with DT-9081 in phase I clinical study in patients with advanced, recurrent or metastatic solid tumors

protein Signaling 14 Ameliorates NAFLD through Activating cAMP-AMPK Signaling by Targeting Giα1/3 APOL1-mediated monovalent cation transport contributes to APOL1-mediated podocytopathy in kidney disease Hepatocyte death by 72% as first-line treatment for patients with advanced gastroenteropancreatic neuroendocrine tumors Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated

PAR4 emerges as a potent oncogene, capable of inducing tumor generation. attenuates PAR2&4-Akt/PKB associations; PAR4 instigated Matrigel invasion and migration in vitro and tumor We propose that Pc(4-4) may serve as a powerful drug not only toward PAR-expressing tumors but also for treating EGFR/erbB-expressing tumors in cases of resistance to traditional therapies.

(CCR9), an organ-specific chemokine receptor, interacts with its exclusive ligand CCL25 to promote tumor Immunohistochemistry staining and RT–qPCR analyses were performed to detect the correlation of CCR9 expression and tumor The effect of CCL25 on the development of SACC in vivo was examined by a xenograft tumor model in nude

Additionally, CXCR4 is expressed by tumor cells in blood malignancies and solid tumors."

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.