ArticleNature2016
Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
155 citing papers in PubMed, 287 citations in OpenAlex.
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- Structure basis for C-C chemokine receptor 4 modulation by orthosteric and allosteric antagonists.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cellular Interactions and Immunometabolic Mechanisms in Heart Failure With Preserved Ejection Fraction: From Molecular Mechanisms to Clinical Evidence.Circulation. Heart failure · 2026Review
- Cancer Manipulates Adjacent Adipose Tissue to Exploit Fatty Acids via HIF-1α/CCL2/PPARα Axis: A Metabolic Circuit to Support Tumor Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Leveraging Targeted Protein Degradation for G Protein-Coupled Receptors: The Development of CCR2 Molecular Degraders.Journal of medicinal chemistry · 2025Article
- Structure-guided design and engineering of a biparatopic antibody targeting CCR2 in triple negative breast cancer.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- CCL2/CCR2 signaling pathway in tumorigenesis and metastasis (Review).Oncology letters · 2025Review
- Epitope analysis of an anti-mouse CCR1 monoclonal antibody S15040E using flow cytometry.Biochemistry and biophysics reports · 2025Article
- Combining AlphaFold with Focused Virtual Library Design in the Development of Novel CCR2 and CCR5 Antagonists.Journal of chemical information and modeling · 2025Article
- Structure-based design of orthosteric and allosteric CCR2 inhibitors for potential IPF therapy.RSC advances · 2025Article
- Terpene-Based Thiazole Hydrazines as Negative Allosteric Modulators of MRGPRX4: In Vitro Evaluation and Binding Site Analysis.ACS medicinal chemistry letters · 2025Article
- Evaluation of Small-Molecule Binding Site Prediction Methods on Membrane-Embedded Protein Interfaces.Journal of chemical information and modeling · 2025Article
- Identification of a Lipid-Exposed Extrahelical Binding Site for Positive Allosteric Modulators of the Dopamine DACS chemical neuroscience · 2025Article
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- Molecular mechanism of the arrestin-biased agonism of neurotensin receptor 1 by an intracellular allosteric modulator.Cell research · 2025Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer. These disease associations have motivated numerous preclinical studies and clinical trials (see http://www.clinicaltrials.gov) in search of therapies that target the CCR2-chemokine axis. To aid drug discovery efforts, here we solve a structure of CCR2 in a ternary complex with an orthosteric (BMS-681 (ref. 6)) and allosteric (CCR2-RA-[R]) antagonist. BMS-681 inhibits chemokine binding by occupying the orthosteric pocket of the receptor in a previously unseen binding mode. CCR2-RA-[R] binds in a novel, highly druggable pocket that is the most intracellular allosteric site observed in class A G-protein-coupled receptors so far; this site spatially overlaps the G-protein-binding site in homologous receptors. CCR2-RA-[R] inhibits CCR2 non-competitively by blocking activation-associated conformational changes and formation of the G-protein-binding interface. The conformational signature of the conserved microswitch residues observed in double-antagonist-bound CCR2 resembles the most inactive G-protein-coupled receptor structures solved so far. Like other protein-protein interactions, receptor-chemokine complexes are considered challenging therapeutic targets for small molecules, and the present structure suggests diverse pocket epitopes that can be exploited to overcome obstacles in drug design.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.