ArticleCancers2021
Targeting of CXCR4 by the Naturally Occurring CXCR4 Antagonist EPI-X4 in Waldenström's Macroglobulinemia.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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
14 citing papers in PubMed, 23 citations in OpenAlex.
- CXCL12 chemokine dimer signaling modulates acute myelogenous leukemia cell migration through altered receptor internalization.Scientific reports · 2025Article
- CXCR4 Inhibition Enhances the Efficacy of CD19 Monoclonal Antibody-Mediated Extermination of B-Cell Lymphoma.International journal of molecular sciences · 2025Article
- Waldenström macroglobulinemia: a review of pathogenesis, current treatment, and future prospects.Annals of hematology · 2024Review
- Single-cell analysis of MYD88HemaSphere · 2024Article
- Development of N-Terminally Modified Variants of the CXCR4-Antagonistic Peptide EPI-X4 for Enhanced Plasma Stability.Journal of medicinal chemistry · 2023Article
- Peptide Bispecifics Inhibiting HIV-1 Infection by an Orthogonal Chemical and Supramolecular Strategy.Bioconjugate chemistry · 2023Article
- CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment.Journal of cancer research and clinical oncology · 2023Review
- Development of a New Class of CXCR4-Targeting Radioligands Based on the Endogenous Antagonist EPI-X4 for Oncological Applications.Journal of medicinal chemistry · 2023Article
- Advanced EPI-X4 Derivatives Covalently Bind Human Serum Albumin Resulting in Prolonged Plasma Stability.International journal of molecular sciences · 2022Article
- The Use of Bruton Tyrosine Kinase Inhibitors in Waldenström's Macroglobulinemia.Journal of personalized medicine · 2022Review
- An Extended Prognostic Index of the ISSWM Score Based on Thyroid Complications in Waldenström Macroglobulinemia/Lymphoplasmacytoid Lymphoma.Frontiers in oncology · 2022Article
- Article
- Computational modeling and experimental validation of the EPI-X4/CXCR4 complex allows rational design of small peptide antagonists.Communications biology · 2021Article
- Absence of the CXCR4 antagonist EPI-X4 from pharmaceutical human serum albumin preparations.Journal of translational medicine · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
CXCR4 expression and downstream signaling have been identified as key factors in malignant hematopoiesis. Thus, up to 40% of all patients with Waldenström's macroglobulinemia (WM) carry an activating mutation of CXCR4 that leads to a more aggressive clinical course and inferior outcome upon treatment with the Bruton's tyrosine kinase inhibitor ibrutinib. Nevertheless, little is known about physiological mechanisms counteracting CXCR4 signaling in hematopoietic neoplasms. Recently, the endogenous human peptide EPI-X4 was identified as a natural CXCR4 antagonist that effectively blocks CXCL12-mediated receptor internalization and suppresses the migration and invasion of cancer cells towards a CXCL12 gradient. Here, we demonstrate that EPI-X4 efficiently binds to CXCR4 of WM cells and decreases their migration towards CXCL12. The CXCR4 inhibitory activity of EPI-X4 is accompanied by reduced expression of genes involved in MAPK signaling and energy metabolism. Notably, the anti-WM activity of EPI-X4 could be further augmented by the rational design of EPI-X4 derivatives showing higher binding affinity to CXCR4. In summary, these data demonstrate that a naturally occurring anti-CXCR4 peptide is able to interfere with WM cell behaviour, and that optimized derivatives of EPI-X4 may represent a promising approach in suppressing growth promoting CXCR4 signaling in WM.
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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 Socratic graph.