ArticleThe Journal of biological chemistry2010
The peptidomimetic CXCR4 antagonist TC14012 recruits beta-arrestin to CXCR7: roles of receptor domains.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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
45 citing papers in PubMed, 84 citations in OpenAlex.
- Induction of C-X-C chemokine receptor type 7 (CXCR7) switches stromal cell-derived factor-1 (SDF-1) signaling and phagocytic activity in macrophages linked to atherosclerosis.The Journal of biological chemistry · 2013Trial
- Regulation of the chemokine receptors CXCR4 and ACKR3 by receptor activity-modifying proteins.The Journal of biological chemistry · 2025Article
- Crosstalk between purinergic receptor P2YCellular and molecular life sciences : CMLS · 2024Article
- CXCR7 Agonist TC14012 Improves Angiogenic Function of Endothelial Progenitor Cells via Activating Akt/eNOS Pathway and Promotes Ischemic Angiogenesis in Diabetic Limb Ischemia.Cardiovascular drugs and therapy · 2023Article
- Effects of Small Molecule Ligands on ACKR3 Receptors.Molecular pharmacology · 2022Article
- Suppressing the activity ofTranslational pediatrics · 2022Article
- A Scintillation Proximity Assay for Real-Time Kinetic Analysis of Chemokine-Chemokine Receptor Interactions.Cells · 2022Article
- Review
- Review
- Emerging Roles of the Atypical Chemokine Receptor 3 (ACKR3) in Cardiovascular Diseases.Frontiers in endocrinology · 2022Review
- Ackr3-Venus knock-in mouse lights up brain vasculature.Molecular brain · 2021Article
- GPCR Pharmacological Profiling of Aaptamine from the Philippine SpongeMolecules (Basel, Switzerland) · 2021Article
- Smooth Muscle Specific Ablation of CXCL12 in Mice Downregulates CXCR7 Associated with Defective Coronary Arteries and Cardiac Hypertrophy.International journal of molecular sciences · 2021Article
- CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor.Scientific reports · 2021Article
- Advances in CXCR7 Modulators.Pharmaceuticals (Basel, Switzerland) · 2020Review
- The Role of the CXCL12/CXCR4/CXCR7 Chemokine Axis in Cancer.Frontiers in pharmacology · 2020Review
- CXCR7/ACKR3-targeting ligands interfere with X7 HIV-1 and HIV-2 entry and replication in human host cells.Heliyon · 2018Article
- Ligand-specific conformational transitions and intracellular transport are required for atypical chemokine receptor 3-mediated chemokine scavenging.The Journal of biological chemistry · 2018Article
- Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle.Open biology · 2018Article
- CXCR7 Targeting and Its Major Disease Relevance.Frontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
CXCR7 is an atypical chemokine receptor that signals through β-arrestin in response to agonists without detectable activation of heterotrimeric G-proteins. Its cognate chemokine ligand CXCL12 also binds CXCR4, a chemokine receptor of considerable clinical interest. Here we report that TC14012, a peptidomimetic inverse agonist of CXCR4, is an agonist on CXCR7. The potency of β-arrestin recruitment to CXCR7 by TC14012 is much higher than that of the previously reported CXCR4 antagonist AMD3100 and differs only by one log from that of the natural ligand CXCL12 (EC(50) 350 nM for TC14012, as compared with 30 nM for CXCL12 and 140 μM for AMD3100). Moreover, like CXCL12, TC14012 leads to Erk 1/2 activation in U373 glioma cells that express only CXCR7, but not CXCR4. Given that with TC14012 and AMD3100 two structurally unrelated CXCR4 antagonists turn out to be agonists on CXCR7, this likely reflects differences in the activation mechanism of the arrestin pathway by both receptors. To identify the receptor domain responsible for these opposed effects, we investigated CXCR4 and CXCR7 C terminus-swapping chimeras. Using quantitative bioluminescence resonance energy transfer, we find that the CXCR7 receptor core formed by the seven-transmembrane domains and the connecting loops determines the agonistic activity of both TC14012 and AMD3100. Moreover, we find that the CXCR7 chimera bearing the CXCR4 C-terminal constitutively associates with arrestin in the absence of ligands. Our data suggest that the CXCR4 and CXCR7 cores share ligand-binding surfaces for the binding of the synthetic ligands, indicating that CXCR4 inhibitors should be tested also on CXCR7.
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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.