ArticleThe Journal of biological chemistry2015
Dual targeting of the chemokine receptors CXCR4 and ACKR3 with novel engineered chemokines.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
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.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- Elevated conformational dynamics makes ACKR3 activation-prone and G protein-incompetent.bioRxiv : the preprint server for biology · 2026Article
- Rules of engagement: Determinants of chemokine receptor activation and selectivity by CCL27 and CCL28.The Journal of biological chemistry · 2025Article
- Noncanonical roles of chemokine regions in CCR9 activation revealed by structural modeling and mutational mapping.Nature communications · 2025Article
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- ACKR3-arrestin2/3 complexes reveal molecular consequences of GRK-dependent barcoding.bioRxiv : the preprint server for biology · 2023Article
- Computational design of dynamic receptor-peptide signaling complexes applied to chemotaxis.Nature communications · 2023Article
- Modular cytokine receptor-targeting chimeras for targeted degradation of cell surface and extracellular proteins.Nature biotechnology · 2023Article
- Insights into innate immune activation via PS-ASO-protein-TLR9 interactions.Nucleic acids research · 2022Article
- Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias.Science advances · 2022Article
- A Scintillation Proximity Assay for Real-Time Kinetic Analysis of Chemokine-Chemokine Receptor Interactions.Cells · 2022Article
- Chemokine-Driven Migration of Pro-Inflammatory CD4Frontiers in immunology · 2022Review
- Engineered Cytokines for Cancer and Autoimmune Disease Immunotherapy.Advanced healthcare materials · 2021Review
- Latest update on chemokine receptors as therapeutic targets.Biochemical Society transactions · 2021Review
- The N-terminal length and side-chain composition of CXCL13 affect crystallization, structure and functional activity.Acta crystallographica. Section D, Structural biology · 2020Article
- Functional anatomy of the full-length CXCR4-CXCL12 complex systematically dissected by quantitative model-guided mutagenesis.Science signaling · 2020Article
- Differential activity and selectivity of N-terminal modified CXCL12 chemokines at the CXCR4 and ACKR3 receptors.Journal of leukocyte biology · 2020Article
- A negative-feedback loop maintains optimal chemokine concentrations for directional cell migration.Nature cell biology · 2020Article
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Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The chemokine CXCL12 and its G protein-coupled receptors CXCR4 and ACKR3 are implicated in cancer and inflammatory and autoimmune disorders and are targets of numerous antagonist discovery efforts. Here, we describe a series of novel, high affinity CXCL12-based modulators of CXCR4 and ACKR3 generated by selection of N-terminal CXCL12 phage libraries on live cells expressing the receptors. Twelve of 13 characterized CXCL12 variants are full CXCR4 antagonists, and four have Kd values <5 nm. The new variants also showed high affinity for ACKR3. The variant with the highest affinity for CXCR4, LGGG-CXCL12, showed efficacy in a murine model for multiple sclerosis, demonstrating translational potential. Molecular modeling was used to elucidate the structural basis of binding and antagonism of selected variants and to guide future designs. Together, this work represents an important step toward the development of therapeutics targeting CXCR4 and ACKR3.
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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.