CCR2 vs CCR1 scavenging signatures CCR1 is constitutively phosphorylated, constitutively interacts with In line, β-Arrestin KO cells showed a major reduction in CCL14 scavenging by CCR1, in contrast with a on CCR1, in contrast with CCR2, indicating that β-arrestin regulates scavenging and signaling of CCR1 to a greater extent than CCR2. In monocytes and dendritic cells exposed to treatments mimicking inflammation, CCR1, CCR2, and CCR5 switch

CCR2, CXCR2, CXCR3, and CX3CR1) (Cardona, A. E., et al. 2008). other chemokine scavenger receptors that where shown to couple to GRKs, β-arrestins, or both such as CCR1 CCR1 is constitutively phosphorylated, constitutively interacts with β-arrestin2, and constitutively Interestingly, in monocytes and dendritic cells exposed to treatments mimicking inflammation, CCR1, CCR2 , and CCR5 switch purely to scavenging (D'Amico G. et al. 2000), becoming incapable of promoting cell

The anti-CCR4 antibody mogamulizumab has also been approved in Japan and by the FDA for the treatment , CCR5, CCR6, CCR7, and CXCR3) and so inhibition of this process through blockade of a single receptor An example is CCL5 which binds to CCR1, CCR3 and CCR5, and induces different patterns of receptor recycling where CCR5 recycles back to the cell surface (Mack et al. 1998), CCR3 is partially restored to the cell surface and partially targeted to lysosomes (Zimmermann, Conkright, and Rothenberg 1999) and CCR1 does

The road map of CCR5 and CCR2 activation The structure of CCR5 has been studied in complex with various Biased Agonism – CCR1 as a model CKR Three active-state structures of CCR1 have been characterized, all The structural analysis of CCR1 demonstrates how the interaction or absence of interaction with a specific signaling or not, although the precise molecular signature responsible for G-protein activation by CCR1 However, comparing CCR6 with closely related receptors, CCR7 and CCR9, in their inactive states offers

CCR5 O-glycosylation, which is under investigation in this study, also plays a major role in promoting Probing the modulation of O-glycosylation and tyrosine sulfation on CCR5 and CCR1 function In this study evaluate the effects of O-glycosylation and tyrosine sulfation modulation on the chemokine receptors CCR1 and CCR5 pharmacology. CHO GalNAc-T knock-outs transfected with CCR5.

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

ligand DLL4 Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5 Chemokine Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant Methods & Updates

Fluorophore-Labeled Pyrrolones Targeting the Intracellular Allosteric Binding Site of the Chemokine Receptor CCR1

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 of CCR2 pharmacology."

Here, we investigated this issue in living cells for the CC chemokine receptor 5 (CCR5), a major receptor We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric In particular, agonist stimulation restricted the mobility of CCR5 and led to its clustering, a feature

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

September 2022 CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma via the PI3K/AKT signaling pathway "Background CC chemokine receptor 9 (CCR9), an organ-specific However, the effect of CCR9 on salivary adenoid cystic carcinoma (SACC) malignant behavior remains unknown This study aimed to investigate the specific molecular mechanism by which CCR9/CCL25 modulates malignant Vercirnon was used as an inhibitor of CCR9, and LY294002 was used as an inhibitor of the PI3K/AKT pathway

Starting from vercirnon, an intracellular C-C chemokine receptor type 9 (CCR9) antagonist and previous for the treatment of Crohn's disease, we developed a chemical biology toolbox targeting the IABS of CCR9 membrane-based setup and in living cells, we discovered a 4-aminopyrimidine analogue as a new intracellular CCR9 To chemically induce CCR9 degradation, we then developed the first PROTAC targeting the IABS of GPCRs In a proof-of-principle study, we succeeded in showing that our CCR9-PROTAC is able to reduce CCR9 levels

Figure 3: In a single discovery campaign (CCR5 is shown as an example), Orion’s PROcisionXᵀᴹ platform Figure 4: Payload delivery using Orion’s superagonist analogs on target cells expressing CCR5. 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

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

Oncology and Immunology Characterization, expressional and evolutionary analysis of five fish-specific CCRs (CCR4La, CCR4Lc, CCR12a1, CCR12a2, and CCR12b) in largemouth bass (Micropterus salmoides) The pyruvate-GPR31 Receptors Investigating the Effect of GLU283 Protonation State on the Conformational Heterogeneity of CCR5

Insights into GPCR Function Cholesterol Biases the Conformational Landscape of the Chemokine Receptor CCR3 A key GPCR phosphorylation motif discovered in arrestin2⋅CCR5 phosphopeptide complexes.

Development of a NanoBRET Assay Platform to Detect Intracellular Ligands for the Chemokine Receptors CCR6 and CXCR1 Reviews, GPCRs, and more International Union of Basic and Clinical Pharmacology CXV: The Class

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

GPCR Partner, Domain Therapeutics, for their nomination of the best-in-class CCR8 antibody candidate, Domain Therapeutics announces nomination of best-in-class CCR8 antibody candidate, DT-7012, further strengthening

GPCRs in Oncology and Immunology CCR6 as a Potential Target for Therapeutic Antibodies for the Treatment

Workflow Domain Therapeutics Strengthens Its Intellectual Property for Its Series of Treg Depleting anti-CCR8

Showcase in Tokyo, Japan, organized by LINK-J Jounce takes the cash under amended deal with Gilead on anti-CCR8

Cholesterol Biases the Conformational Landscape of the Chemokine Receptor CCR3: A MAS SSNMR-Filtered

CCL5-producing migratory dendritic cells guide CCR5+ monocytes into the draining lymph nodes.

α2A-adrenergic receptor in intestinal stem cells to exacerbate colitis The EBI2 receptor is coexpressed with CCR5

transduction NPFF stimulates human ovarian cancer cell invasion by upregulating MMP-9 via ERK1/2 signaling CCR7