ArticleCommunications biology2021
Biased action of the CXCR4-targeting drug plerixafor is essential for its superior hematopoietic stem cell mobilization.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Plerixafor Engages β-Arrestin-Dependent CXCR4 Signaling to Promote Melanogenesis via β-Catenin-MITF Activation.Current issues in molecular biology · 2026Article
- C-X-C chemokine receptor type 4 (CXCR4) antagonism in precision oncology: Clinical applications and future directions.Cancer pathogenesis and therapy · 2026Review
- Pharmacological modulation of CXCL12/CXCR4/ACKR3 for brain disorders - an overview.Cell communication and signaling : CCS · 2026Review
- Inhibition of Cxcr4 chemokine receptor signaling improves habituation learning in a zebrafish model of neurofibromatosis.Disease models & mechanisms · 2026Article
- Targeting of Kaposi's sarcoma-associated herpesvirus by immunotoxins directed against the viral G protein-coupled receptor, ORF74.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Deciphering the Interlinked CXCR4-Mediated Feedback Loop Among Signaling Pathways in Diabetic Wound Healing.Current diabetes reviews · 2026Review
- Molecular Insights into Bromocriptine Binding to GPCRs Within Histamine-Linked Signaling Networks: Network Pharmacology, Pharmacophore Modeling, and Molecular Dynamics Simulation.International journal of molecular sciences · 2025Article
- GPCR drug discovery: new agents, targets and indications.Nature reviews. Drug discovery · 2025Review
- SERCA-mediated endoplasmic reticulum stress facilitates hematopoietic stem cell mobilization.Stem cell research & therapy · 2025Article
- CXC Chemokine Ligand 12 Facilitates Gi Protein Binding to CXC Chemokine Receptor 4 by Stabilizing Packing of the Proline-Isoleucine-Phenylalanine Motif: Insights from Automated Path Searching.Journal of the American Chemical Society · 2025Article
- Translation Research in Therapeutic Approaches from Conventional to Novel Nano-therapeutics for Rheumatoid Arthritis Treatment.Current rheumatology reviews · 2025Review
- CXCR4 antagonism corrects neutrophil abnormalities and reduces pneumonia severity in a pharmacological mouse model of CXCR2 loss-of-function-mediated neutropenia.Frontiers in immunology · 2025Article
- Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.Clinical and translational science · 2024Article
- Predictive factors for peripheral blood stem cell mobilization in multiple myeloma in the era of novel therapies: A single-center experience.Cancer medicine · 2024Article
- CXCR4 antagonism ameliorates leukocyte abnormalities in a preclinical model of WHIM syndrome.Frontiers in immunology · 2024Article
- Biological and mutational analyses of CXCR4-antagonist interactions and design of new antagonistic analogs.Bioscience reports · 2023Article
- Triazolothiadiazine derivative positively modulates CXCR4 signaling and improves diabetic wound healing.Biochemical pharmacology · 2023Article
- Inhibition ofInternational journal of molecular sciences · 2023Article
- Identification of a Salt Bridge That Is Functionally Important for Chemokine Receptor CXCR1 but not CXCR2.ACS pharmacology & translational science · 2023Article
- Drug-based mobilisation of mesenchymal stem/stromal cells improves cardiac function post myocardial infarction.Disease models & mechanisms · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
Abstract
Following the FDA-approval of the hematopoietic stem cell (HSC) mobilizer plerixafor, orally available and potent CXCR4 antagonists were pursued. One such proposition was AMD11070, which was orally active and had superior antagonism in vitro; however, it did not appear as effective for HSC mobilization in vivo. Here we show that while AMD11070 acts as a full antagonist, plerixafor acts biased by stimulating β-arrestin recruitment while fully antagonizing G protein. Consequently, while AMD11070 prevents the constitutive receptor internalization, plerixafor allows it and thereby decreases receptor expression. These findings are confirmed by the successful transfer of both ligands' binding sites and action to the related CXCR3 receptor. In vivo, plerixafor exhibits superior HSC mobilization associated with a dramatic reversal of the CXCL12 gradient across the bone marrow endothelium, which is not seen for AMD11070. We propose that the biased action of plerixafor is central for its superior therapeutic effect in HSC mobilization.
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