ArticleBritish journal of pharmacology2014
Determination of the binding mode for the cyclopentapeptide CXCR4 antagonist FC131 using a dual approach of ligand modifications and receptor mutagenesis.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 46 citations in OpenAlex.
- Noncanonical roles of chemokine regions in CCR9 activation revealed by structural modeling and mutational mapping.Nature communications · 2025Article
- Targeting the chemokine receptor CXCR4 for cancer therapies.Biomarker research · 2025Review
- Targeting the CXCR4/CXCL12 Axis in Cancer Therapy: Analysis of Recent Advances in the Development of Potential Anticancer Agents.Molecules (Basel, Switzerland) · 2025Review
- Third intracellular loop of HCMV US28 is necessary for signaling and viral reactivation.Journal of virology · 2025Article
- Radiosynthesis and preclinical evaluation of aEJNMMI radiopharmacy and chemistry · 2024Article
- Biological and mutational analyses of CXCR4-antagonist interactions and design of new antagonistic analogs.Bioscience reports · 2023Article
- Profiling of basal and ligand-dependent GPCR activities by means of a polyvalent cell-based high-throughput platform.Nature communications · 2023Article
- Structural Basis of the Binding Mode of the Antineoplastic Compound Motixafortide (BL-8040) in the CXCR4 Chemokine Receptor.International journal of molecular sciences · 2023Article
- Discovery of Bis-Imidazoline Derivatives as New CXCR4 Ligands.Molecules (Basel, Switzerland) · 2023Article
- At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer.Journal of leukocyte biology · 2021Review
- Advanced fluorescence microscopy reveals disruption of dynamic CXCR4 dimerization by subpocket-specific inverse agonists.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Internal water channel formation in CXCR4 is crucial for GCommunications chemistry · 2020Article
- Functional anatomy of the full-length CXCR4-CXCL12 complex systematically dissected by quantitative model-guided mutagenesis.Science signaling · 2020Article
- Selective Allosteric Modulation of N-Terminally Cleaved, but Not Full Length CCL3 in CCR1.ACS pharmacology & translational science · 2019Article
- Validation of [EJNMMI research · 2019Article
- Assessment of Copper Nanoclusters for Accurate in Vivo Tumor Imaging and Potential for Translation.ACS applied materials & interfaces · 2019Article
- Structural Analysis of Chemokine Receptor-Ligand Interactions.Journal of medicinal chemistry · 2017Review
- Molecular Mechanism of Action for Allosteric Modulators and Agonists in CC-chemokine Receptor 5 (CCR5).The Journal of biological chemistry · 2016Article
- CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks.Oncogene · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe cyclopentapeptide FC131 (cyclo(-L-Arg(1) -L-Arg(2) -L-2-Nal(3) -Gly(4) -D-Tyr(5) -)) is an antagonist at the CXC chemokine receptor CXCR4, which plays a role in human immunodeficiency virus infection, cancer and stem cell recruitment. Binding modes for FC131 in CXCR4 have previously been suggested based on molecular docking guided by structure-activity relationship (SAR) data; however, none of these have been verified by in vitro experiments. EXPERIMENTAL APPROACH: Heterologous (125) I-12G5-competition binding and functional assays (inhibition of CXCL12-mediated activation) of FC131 and three analogues were performed on wild-type CXCR4 and 25 receptor mutants. Computational modelling was used to rationalize the experimental data. KEY
resultsThe Arg(2) and 2-Nal(3) side chains of FC131 interact with residues in TM-3 (His(113) , Asp(171) ) and TM-5 (hydrophobic pocket) respectively. Arg(1) forms charge-charge interactions with Asp(187) in ECL-2, while D-Tyr(5) points to the extracellular side of CXCR4. Furthermore, the backbone of FC131 interacts with the chemokine receptor-conserved Glu(288) via two water molecules. Intriguingly, Tyr(116) and Glu(288) form a H-bond in CXCR4 crystal structures and mutation of either residue to Ala abolishes CXCR4 activity. CONCLUSIONS AND IMPLICATIONS: Ligand modification, receptor mutagenesis and computational modelling approaches were used to identify the binding mode of FC131 in CXCR4, which was in agreement with binding modes suggested from previous SAR studies. Furthermore, insights into the mechanism for CXCR4 activation by CXCL12 were gained. The combined findings will facilitate future design of novel CXCR4 antagonists.
Indexed as
Identifiers
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.