August 2022 Dopamine D 1 receptor-mediated β-arrestin signaling: Insight from pharmacology, biology, of biased compounds as both research tools and novel drugs. Although this field has exploded during the past two decades, it is only recently that highly β-arrestin biased ligands for the dopamine D1 receptor were reported. Read more at the source #DrGPCR #GPCR #IndustryNews

Neuropeptides and their receptors have been documented in many hemipteran insects, but the differences precursors and 48 putative neuropeptide G protein-coupled receptor (GPCR) genes were identified in D. Additionally, we discovered that the neuropeptide signaling systems of Sternorrhyncha were very different research provides more knowledge on neuropeptide systems and sets the groundwork for the creation of novel D. Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened "The oncogenic G-protein-coupled receptor (GPCR) Smoothened wing imaginal disc as a model. Together, these results link the morphogenetic effects of HH to the apico-basal distribution of SMO and Read more at the source #DrGPCR #GPCR #IndustryNews

D1R, D2LR, D3R, and D4R, vasopressin V1AR, and serotonin 5-HT1AR are noted in various neurodegenerative diseases (NDDs). Radioligand binding assays revealed considerable binding of kurarinone on D1R, D2LR, and D4R. Molecular docking displayed low binding energies during the intermolecular interactions of kurarinone with the key residues of the deep orthosteric binding pocket and the extracellular loops of D1R, D2LR

whether melatonin receptors are expressed on airway smooth muscle; whether they regulate intracellular cyclic We detected the mRNA and protein expression of the melatonin MT2 but not the MT1 receptor in native human Although melatonin by itself did not induce an initial [Ca2+]i increase and airway contraction, melatonin

Arrb1 deficiency suppressed HBx-induced hepatocellular carcinogenesis in several mouse models. Furthermore, knockdown of ARRB1 blocked HBx-induced macroautophagic/autophagic flux and disrupted the Our results demonstrate that ARRB1 plays a critical role in HBV-related HCC via modulating autophagy 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

April 2022 Sosei Heptares Confirms Senior Leadership Changes to Drive the Company Through the Next Stage of its Evolution "New team focused on expanding its GPCR-focused structure-based drug design platform Chris Cargill appointed as President and Chief Executive Officer • Dr. ., and Head of UK R&D Tokyo, Japan and Cambridge, UK, 24 March 2022 – Sosei Group Corporation (“the Read more at the source #DrGPCR #GPCR #IndustryNews

GPR15 signals through the Gi/o pathway to decrease intracellular cyclic adenosine 3',5'-monophosphate Here, GPR15L(25-81) and GPR15L(71-81) are used as pharmacological tool compounds to delineate the GPR15 The potencies of both peptides toward each Gi/o subtype have been determined. Read more at the source #DrGPCR #GPCR #IndustryNews

Here, we demonstrate identification of a pleckstrin-homology (PH)-binding motif within PAR4, critical Point mutations are in the C-tail of PAR4 PH-binding domain; F347 L and D349A, but not E346A, abrogate Pc(4-4), a lead backbone cyclic peptide, was selected out of a mini-library, directed toward PAR2&4 PH-binding We propose that Pc(4-4) may serve as a powerful drug not only toward PAR-expressing tumors but also for Read more at the source #DrGPCR #GPCR #IndustryNews

Using two indices of cell growth, we show that PI3K inhibition and depletion of GRK2 expression produced Conversely, the GRK2 inhibitor compound 101 did not affect vasoconstrictor-driven Akt phosphorylation Moreover, GRK2 knockdown prevented endothelin-1 and angiotensin-II from increasing cyclin D1 expression These data suggest GRK2 expression is essential to facilitate vasoconstrictor-driven VSMC proliferation Considering VSMC GRK2 expression increases early in the development of hypertension, this highlights

October 2022 GPR125 (ADGRA3) is an autocleavable adhesion GPCR that traffics with Dlg1 to the basolateral seven-transmembrane domain. The cleavage appears to occur at an atypical GPCR proteolysis site within the GAIN domain during an early with the cell polarity protein Dlg1. Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the newsletter HERE

October 2022 Novel Therapies for Cardiometabolic Disease: Recent Findings in Studies with Hormone Peptide-Derived G Protein Coupled Receptor Agonists "The increasing prevalence of obesity and type 2 diabetes (T2DM) The present review describes novel findings regarding the complex biology of the preproglucagon-derived hormones, their signaling, and the drug development of their analogues, especially those acting as dual Read more at the source #DrGPCR #GPCR #IndustryNews

2 (PAR2) is a G-protein-coupled receptor (GPCR) activated by proteolytic cleavage of its N-terminal domain Once activated, PAR2 is rapidly desensitized and internalized by phosphorylation and β-arrestin recruitment Due to its irreversible activation mechanism, some agonists that rapidly desensitized PAR2 have been markedly elicited an increase in intracellular calcium levels and phosphorylation of MAPKs, but in a delayed Read more at the source #DrGPCR #GPCR #IndustryNews

and the substituted amphetamine 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), is receiving renewed and substance use disorders. However, the pharmacokinetic properties of DOI differed among sexes - brain and plasma concentrations of DOI were lower 30 and 60 min after drug administration in female as compared to male C57BL/6J mice Together, these results suggest strain-dependent and sex-related differences in the behavioral and pharmacokinetic

noticeably, these interactions are not limited to members of the same family, but involve receptors as diverse We will discuss recent evidence as well as what we consider as emerging areas to explore; from the signalling and signaling pathways is only beginning to be explored and represents a novel mechanism providing diversity to receptor function and play important roles in physiology and disease." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "The prefrontal cortex (PFC) is a hub for cognitive control, and dopamine profoundly influences In other brain regions, astrocytes sense diverse neurotransmitters and neuromodulators and, in turn, cortex, which show differential responsiveness to locomotion. Further, we describe dopamine-triggered regulation of extracellular ATP at PFC astrocyte territories. Read more at the source #DrGPCR #GPCR #IndustryNews

Dysfunction of B2R is also closely related to cancers and hereditary angioedema (HAE). of B2R, which shed light on structure-based drug design for the treatment of B2R-related diseases. In this review, we summarize the structure and function of B2R in relation to drug discovery and discuss future research directions to elucidate the remaining unknown functions of B2R dimerization." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Alzheimer's disease (AD) is the most common dementia in the elderly and its increasing 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

October 2022 Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent skin dysbiosis and bacterial infection "Healthy skin maintains a diverse microbiome and a potent immune Here, we discovered that the epithelial-cell-derived antimicrobial peptides defensins activated orphan We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a Def and Mrgpra2 mutant animals both exhibited skin dysbiosis, with reduced microbial diversity and expansion

October 2022 "The activity of dopamine neurons is dependent on both intrinsic properties and afferent KEY POINTS: Inhibitory D2 and GABAB receptors modulate dopamine neuron activity through shared G protein-coupled Activation of either D2 or GABAB receptors also acutely desensitized the GIRK channel current induced by D2 receptor activation that rapidly recovers following termination of desensitizing stimulus. Read more at the source #DrGPCR #GPCR #IndustryNews

UCPs have been hotly contested, and the involvement of UCPs in the pathogenesis and progression of diabetes triggered by superoxide and then reduce mitochondrial free radical production, potentially protecting diabetes Objectives: The objectives of the study are to find out the newest ways to treat diabetes mellitus through Read more at the source #DrGPCR #GPCR #IndustryNews

of drugs with superior efficacy and reduced side effects in heart disease, pain management, and neuropsychiatric disorders. However, Gpr3-deficient mice display several adverse phenotypes, including elevated anxiety-like behavior In contrast to Gpr3-deficient mice, G protein-biased GPR3 mice do not display elevated anxiety levels We further determined that G protein-biased signaling reduces soluble Aβ levels and leads to a decrease

Promising preclinical data supports the applicability of CB2 activation in autoimmune and inflammatory diseases, pain, neurodegeneration, and osteoporosis. A diverse pharmacopoeia of cannabinoid ligands is available, which has led to considerable advancements A number of strategies have been applied to develop CB2 ligands to achieve closer to 'drug-like' properties Read more at the source #DrGPCR #GPCR #IndustryNews

Dopamine receptors are involved in the modulation of fundamental physiological functions, and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity We demonstrate that azodopa activates D1-like receptors in vitro in a light-dependent manner. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wild-type animals

While traditional drug discovery programs have focused on the development of ligands targeting the binding Recent advances in the structure determination of GPCRs bound to different types of allosteric modulators and development of allosteric modulators as novel therapeutic candidates. discovery and design." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Case Report of a Juvenile Patient with Autism Spectrum Disorder with a Novel Combination (ASD) and attention deficit/hyperactivity disorder (ADHD). , though no intellectual disability was present. but responded positively to 3 mg per day of the atypical neuroleptic drug aripiprazole. Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 GPCR Agonist-to-Antagonist Conversion: Enabling the Design of Nucleoside Functional Switches , inflammation, cancer, and central nervous system disorders. Herein, we demonstrate that a thiophene modification at the C8 position in the common adenine scaffold This approach can expand the repertoire of adenosine receptor antagonists that can be designed based Read more at the source #DrGPCR #GPCR #IndustryNews

Promising preclinical data support the applicability of CB2 activation in autoimmune and inflammatory diseases, pain, neurodegeneration, and osteoporosis. A diverse pharmacopeia of cannabinoid ligands is available, which has led to considerable advancements A number of strategies have been applied to develop CB2 ligands to achieve closer to 'drug-like' properties Read more at the source #DrGPCR #GPCR #IndustryNews