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October 2022 "CXCR1 and CXCR2 chemokine receptors, mainly activated by interleukin 8 (IL-8 or CXCL8), Much focus is currently being directed towards CXCR1/2 inhibitors, as these receptors primarily induce CXCR1/2 inhibitors show beneficial effects in various animal models of CVD. Based on these encouraging results, testing CXCR1/2 inhibitors in clinical trials could be of a great

August 2022 "CXCR1 and CXCR2 chemokine receptors, mainly activated by interleukin 8 (IL-8 or CXCL8), Much focus is currently being directed towards CXCR1/2 inhibitors, as these receptors primarily induce CXCR1/2 inhibitors show beneficial effects in various animal models of CVD. Based on these encouraging results, testing CXCR1/2 inhibitors in clinical trials could be of a great

CCR2, CXCR2, CXCR3, and CX3CR1) (A. E. Cardona et al. 2008). Molecular signature of CCR2 scavenging - no G proteins, no GRKs, no arrestins, and no clathrin Chemokine In this study, the molecular signature of CCR2 scavenging role is investigated. CCR2 canonical signaling requires the activation of Gαiβγ, followed by phosphorylation of the receptor CCR2 inhibition leads to inhibition of scavenging and elevated plasma levels of CCL2 (Y.

CCR2, CXCR2, CXCR3, and CX3CR1) (Cardona, A. E., et al. 2008). CCR2 is an example of a dual-function receptor that directly regulates both cell migration and scavenging This study revealed that CCR2 scavenging is independent of G proteins, GRKs, arrestins, as well as clathrin Interestingly, in monocytes and dendritic cells exposed to treatments mimicking inflammation, CCR1, CCR2 For instance, CCR2 inhibition leads to inhibition of scavenging and elevated plasma levels of CCL2 (Aiello

GPCRs in Oncology and Immunology Expanding role of CXCR2 and therapeutic potential of CXCR2 antagonists

to the biased signaling generated by three endogenous ligands of the GPCR CXC chemokine receptor 3 (CXCR3 The signaling profile of CXCR3 changes as it traffics from the plasma membrane to endosomes in a ligand-specific In a mouse model of contact hypersensitivity, β-arrestin-biased CXCR3-mediated inflammation is dependent demonstrates that differential subcellular signaling is critical to the overall biased response observed at CXCR3

C-X-C motif chemokine receptor 4 (CXCR4), a G-protein-coupled receptor (GPCR), has one identified natural Evidence demonstrated that the ligation of SDF-1 to CXCR4 initiates several intracellular signaling pathways Additionally, CXCR4 is expressed by tumor cells in blood malignancies and solid tumors."

Enable Target Engagement Studies for the Intracellular Allosteric Binding Site of the Chemokine Receptor CXCR2

., 2018) which agonizes GPR84 but, interestingly, blocks the chemokine receptor CXCR2 and the adenosine

ligands targeting the intracellular allosteric binding site (IABS) of the CC chemokine receptor 2 (CCR2 Starting from previously reported intracellular CCR2 antagonists, several tetramethylrhodamine (TAMRA to probe binding to the IABS of CCR2. By means of these studies, we developed 14 as a fluorescent CCR2 ligand, enabling cell-free as well as of CCR2 pharmacology."

OB-004 is a GPCR targeted protein analog of CCL2 that targets the CCR2 receptor. The CCL2/CCR2 pathway plays an important role in oncology, inflammatory, metabolic, and neurological

G-protein-biased allosteric antagonists are under investigation for several GPCRs, including CCR2, CCR7 , CCR9, CXCR2, and β2AR.

Unculturable Plant Symbiont Systematic assessment of chemokine ligand bias at the human chemokine receptor CXCR2

Activation of Mrgpra2 by defensin triggered neutrophil release of IL-1β and CXCL2 which are vital for

work on Receptor determinants for ß-arrestin functional specificity at C-X-C chemokine receptor 5 (CXCR5 receptors Receptor determinants for ß-arrestin functional specificity at C-X-C chemokine receptor 5 (CXCR5 GPCRs in Oncology and Immunology The GPCR adaptor protein Norbin controls the trafficking of C5aR1 and CXCR4 treatment of alcohol use disorders: Opportunities and hurdles for clinical development Chemokine CXCL13-CXCR5

allosteric and reversible inhibitor of the CCR5 used in HIV therapy; and the small molecule plerixafor, a CXCR4 infiltration of Treg cells which can be driven directly by different receptors (CCR4, CCR5, CCR6, CCR7, and CXCR3 Subsequent reports characterizing small molecule agonists for CXCR3 further substantiated the notion

Discovery and In Vivo Evaluation of ACT-660602: A Potent and Selective Antagonist of the Chemokine Receptor CXCR3 for Autoimmune Diseases "The chemokine receptor CXCR3 is a seven-transmembrane G-protein-coupled receptor describe the iterative optimization of a chemical series culminating in the discovery of the selective CXCR3 LPS-induced lung inflammation model in mice, ACT-660602 led to significantly reduced recruitment of the CXCR3

a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4 The S339fs5 and R334X mutants exhibited significantly increased signaling compared to wild type CXCR4 with S339fs5 having a very high basal level of degradation compared to that of R334X and wild type CXCR4 Moreover, while basal and agonist-promoted degradation of wild type CXCR4 was effectively inhibited by the CXCR4 antagonist TE-14016, this had no effect on the degradation of the WHIM mutants.

distal carboxyl-terminal tail (C-tail), but not proximal, phosphorylation of the chemokine receptor CXCR4 demonstrate by pharmacologic inhibition of GRK2/3-mediated phosphorylation of the chemokine receptor CXCR4 provides evidence that distal C-tail phosphorylation sites specify GRK-βarrestin-mediated signaling by CXCR4

Novel RGS2-Galpha-q Interaction Inhibitors with Anticancer Activity Evolutionary diversity of CXCL16-CXCR6 Development of a NanoBRET Assay Platform to Detect Intracellular Ligands for the Chemokine Receptors CCR6 and CXCR1

C-X-C motif chemokine ligand 12 (CXCL12) has two receptors: C-X-C chemokine motif receptor 4 (CXCR4) known mammalian G α isoforms and have generated a comprehensive map of the G α activation by CXCL12/CXCR4 selective ACKR3 ligands should allow us to better appreciate the unique roles of ACKR3 in the CXCL12/CXCR4

Hartley will also present new data on Orion’s CCR2 antagonist, OB-004, demonstrating the ability of this

Sudarshan Rajagopal, et al. for their finding that GPCR kinases affect biased signaling downstream of CXCR3 agonists of the relaxin-3 receptor GPCR kinases differentially modulate biased signaling downstream of CXCR3

CRS1.5 is an intermediate recognition site between CRS1 and CRS2, first described in the CXCR4-vCCL2 The road map of CCR5 and CCR2 activation The structure of CCR5 has been studied in complex with various The active state structure of CCR2 with its endogenous agonist CCL2, as well as inactive states with

Liang, Niña Caculitan, and Adam W Smith for their research on β2-adrenergic receptor associates with CXCR4 signaling and pain homeostasis GPCRs in Oncology and Immunology The β2-adrenergic receptor associates with CXCR4

fibroblast-like synoviocytes contributes to inflammatory joint pain Regulation of the chemokine receptors CXCR4

Phosphorylation barcodes direct biased chemokine signaling at CXCR3.

Case study: Discovering a CCR2 Antagonist The chemokine receptor CCR2 regulates the recruitment of monocytes Since many inflammatory diseases are driven by inappropriate recruitment of monocytes into tissues, CCR2 Orion’s CCR2 antagonist analog (OB-004), discovered in only 6 months, is considerably more potent than human monocytic cell line, OB-004 demonstrated best-in-class potency versus a group of small molecule CCR2