Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP" Read more at the source #DrGPCR #GPCR #IndustryNews

The advent of AlphaFold2 (AF2) has brought AI applications in drug development to unprecedented heights targets and designing effective drug molecules. development. Despite its transformative potential, AI in drug development faces several challenges. data.

, combined with electrophysiological studies, indicate that CB2 receptors are expressed in specific dopaminergic where novel interventions that move beyond dopamine receptor antagonists are desperately needed. The development of new CB2-related pharmacological and genetic tools, including the first small molecule commonly associated with positive and cognitive deficits." Read more at the source #DrGPCR #GPCR #IndustryNews

TRPM3 expression patterns differ between species and change during development. This complexity makes it difficult to obtain a clear picture of TRPM3 characteristics. 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. Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "As important drug targets, G protein-coupled receptors (GPCRs) play pivotal roles in a wide However, a large portion of GPCR structures remain unsolved due to structural instability. However, the predicted models and experimental structures were different in many aspects including the drug design of GPCRs, which required reliable high-resolution structural information." Read more at the source #DrGPCR #GPCR #IndustryNews

protein-coupled receptors (GPCRs) are the largest family of membrane receptors that serve as the most important drug Classically, GPCR internalization has been considered to lead to receptor desensitization. distinct signal activation. GPCR internalization dynamics, internalization routes, postinternalization fates, and related diseases Read more at the source #DrGPCR #GPCR #IndustryNews

In this study, we found, for the first time, that the expression of GPR110 increased during osteoclastogenesis GPR110 belongs to adhesion GPCR and was the functional receptor of N-docosahexaenoyl ethanolamine (also Considering that synaptamide is the endogenous metabolite of DHA, we hypothesized that DHA may inhibit revealed a pivotal role of GPR110 in the attenuation of osteoclastogenesis by synaptamide but not by DHA Read more at the source #DrGPCR #GPCR #IndustryNews

During Drosophila embryonic salivary gland (SG) invagination, the GPCR ligand Folded gastrulation (Fog ) activates Rho1 signaling to drive apical constriction. Our data support a model wherein Smog regulates distinct myosin pools and actin cytoskeleton in a ligand-dependent manner during epithelial tube formation." Read more at the source #DrGPCR #GPCR #IndustryNews

Opioid receptors (ORs) represent one of the most significant groups of G-protein coupled receptor (GPCR) drug In a constant effort to develop drugs with less side effects, and tools to explore the ORs nature and function, various (poly)pharmacological ligand design approaches have been performed. That is, besides classical ligands, a great number of bivalent ligands (i. e. aiming on two distinct Read more at the source #DrGPCR #GPCR #IndustryNews

The immune system depends on chemokines to direct cell migration during immune surveillance and inflammation , as well as to play vital roles in the development, maturation, and homing of lymphocytes and the development However, an imbalance in the chemokine system can also contribute to various diseases, such as inflammatory Indeed, ACKRs behave as scavenging “decoys” in order to either limit chemokines spatial availability CCR2 is an example of a dual-function receptor that directly regulates both cell migration and scavenging

“The desire to take medicine is perhaps the greatest feature which distinguishes man from animals.” Historically, drug discovery efforts targeting GPCRs focused on G-protein-dependent signaling pathways targeting in drug discovery. utilising different detection technologies. Minireview: targeting GPCR activated ERK pathways for drug discovery.

Considering this, we investigated the role of RGS20 as a potential prognostic marker in 28 different By using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data, our analysis revealed adenocarcinoma: p = 0.004, mesothelioma: p = 0.039, ovarian serous cystadenocarcinoma: p = 0.048); (d) Read more at the source #DrGPCR #GPCR #IndustryNews

During Drosophila embryonic salivary gland (SG) invagination, the GPCR ligand Folded gastrulation (Fog ) activates Rho1 signaling to drive apical constriction. Our data support a model wherein Smog regulates distinct myosin pools and actin cytoskeleton in a ligand-dependent manner during epithelial tube formation." Read more at the source #DrGPCR #GPCR #IndustryNews

Currently, the exact function of the C5aR2 is actively debated in the context of C5aR1, even though both The functional relevance of C5aR2 appears to be context-dependent compared to the C5aR1, which has received enormous attention for its role in both acute and chronic inflammatory diseases. The computational modeling and the 1.5-μs molecular dynamics data presented in the current study are Read more at the source #DrGPCR #GPCR #IndustryNews

This review discusses the specific tissue expression of the components of the chemerin system, and the role of different proteases in regulating the activation and inactivation of chemerin. Methods of identifying and determining the levels of different chemerin forms in both mass and activity with obesity or diabetes, leading to the possibility of using chemerin as a biomarker." Read more at the source #DrGPCR #GPCR #IndustryNews

drives progressive pulmonary fibrosis. then drives its own activation, creating a feed-forward mechanism that propagates myofibroblast differentiation IPF and that TGF-β1 decreases OGR1 expression. In fibroblasts, OGR1 inhibits myofibroblast differentiation and does not contribute to inflammation. Read more at the source #DrGPCR #GPCR #IndustryNews

of inflammatory and fibrotic diseases. (UC) patients and dextran sulfate sodium (DSS)-induced colitis mice. Consistently, GPR84-/- mice are resistant to the development of colitis induced by DSS. that GPR84 may serve as a potential drug target for the treatment of UC." Read more at the source #DrGPCR #GPCR #IndustryNews

We combined in vitro and in situ chemical crosslinking, disulfide pattern analysis, and mutation data with molecular modeling to generate experimentally driven full-length models. A major rearrangement of the HR seems implausible due to the tight arrangement and fixation by disulfide The models are expected to allow for testable hypotheses about signal transduction and drug development Read more at the source #DrGPCR #GPCR #IndustryNews

Yet phospholipid scrambling is not detectable in the resting plasma membrane of mammalian cells that Our previous Markov State Model (MSM) analysis of molecular dynamics simulations of membrane-embedded opsin indicated that phospholipid headgroups traverse a dynamically revealed hydrophilic groove between Read more at the source #DrGPCR #GPCR #IndustryNews

receptor agonists attenuate macrophage IL‐1β expression and eosinophilic inflammation linked to autophagy deficiency Autophagy deficiency in myeloid cells plays a causal role in eosinophilic CRS (ECRS) via macrophage IL Trehalose is a disaccharide sugar with known pro‐autophagy activity and effective in alleviating diverse inflammatory diseases. Read more at the source #DrGPCR #GPCR #IndustryNews

Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP." Read more at the source #DrGPCR #GPCR #IndustryNews

Capturing the dynamics of GPCR activation has always been a challenge because G protein activation in of the events driving G protein activation upon GTP binding. This detailed process provided by the cryo-EM study offers a clear view of these dynamic states, from map for pharmaceutical researchers to design new therapies. With this high-resolution, dynamic view of GPCR activation, scientists can better tackle diseases by

Under the joint research plan, the Danish giant will work with EraCal to identify novel drug targets Although specific details of the collaboration are yet to be released, EraCal has confirmed that the duo will utilise its phenotypic drug discovery platform to identify potential targets." Re ad more at the source #DrGPCR #GPCR #IndustryNews

Boehringer Ingelheim take first steps towards collaborating to unlock orphan targets leveraging InterAx AI driven discovery platform. already successfully applied in projects with biopharmaceutical companies and also used in-house to discover #ai #biotech #systemsbiology #drugdiscovery #gpcr #deeptech #orphandrugs #pharma #partnerships #AI4drugdiscovery " Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Despite the importance of members of the GPCR superfamily as targets of a broad range of and clinical trials to treat idiopathic pulmonary fibrosis are currently ongoing using ligands with differing Although blockade of GPR84 may potentially prove effective also in diseases associated with inflammation structural information, recent developments and use of GPR84 pharmacological tool compounds to study its broader role and biology. " Read more at the source #DrGPCR #GPCR #IndustryNews

Addex and Indivior Extend GABAB Positive Allosteric Modulator Research Collaboration for Substance Use Disorders SIX and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, today announced that its collaboration agreement with Indivior PLC (LON : INDV) for discovering and developing novel oral gamma-aminobutyric acid subtype B (GABAB) positive allosteric modulator (PAM) drug candidates has been extended until March 31, 2023.

Despite the existence of numerous drugs designed for this primary binding site, there are significant Allosteric binding sites on the receptor are those topographically distinct from (do not exhibit any such as liver disease, obesity and diabetes (Secor et al. 2021; Wold and Zhou 2018). , dimerization, phosphorylation, internalization, or desensitization), the same drug acting on the same This variability in drug effects is due to different ligands inducing unique GPCR conformations that

Confo Therapeutics receives €1.7 million VLAIO grant for further research on GPCR modulators for rare diseases The grant should help expand Confo Therapeutic ’s research on G protein-coupled receptor (GPCR) drug candidates. " Read more at the source #DrGPCR #GPCR #IndustryNews