cyclic-cit-peptide-igg-ab CXCR4 peptide antagonists represent a promising class of therapeutic agents targeting the CXC chemokine receptor 4 (CXCR4).作者：MD Galsky·2014·被引用次数：133—This article reports the results of a phase I study designed to evaluate the safety and tolerability of the CXC motif receptor 4 (CXCR4) inhibitor LY2510924 in ... This receptor plays a crucial role in various physiological and pathological processes, including immune cell trafficking, stem cell mobilization, and cancer progression.Discovery and Characterization of an Endogenous CXCR4 ... By blocking the interaction between CXCR4 and its primary ligand, CXCL12 (also known as SDF-1), these antagonists can modulate critical cellular functions, making them valuable tools in research and potential treatments for a range of diseasesIn this study we developed a derivative of theCXCR4 peptide antagonist, T140-2D, that can be labeled easily with the PET isotope copper-64, and thereby enable .... The development of specific CXCR4 peptide antagonists, such as LY2510924 and EPI-X4, is a significant area of ongoing research, aiming to harness their antineoplastic and immunomodulatory properties.
The CXCR4 receptor is a G protein-coupled receptor found on the surface of various cell types, including leukocytes, stem cells, and many cancer cells. Its primary ligand, CXCL12, is secreted by stromal cells in numerous tissues, creating a signaling axis that is vital for normal development and immune surveillance. This CXCR4/CXCL12 axis is implicated in:
* Hematopoiesis and Stem Cell Mobilization: CXCR4 is essential for retaining hematopoietic stem cells (HSCs) in the bone marrow. Antagonizing CXCR4 can lead to the release of these stem cells into the bloodstream, a process utilized in stem cell transplantation.
* Immune Cell Trafficking: The receptor guides the migration of immune cells, influencing inflammatory responses and immune cell distribution throughout the body.
* Cancer Progression: In many cancers, the CXCR4/CXCL12 axis is upregulated, promoting tumor cell survival, proliferation, migration, invasion, and metastasis作者：B Hitchinson·2018·被引用次数：57—AMD3100, an antagonist of the chemokine receptor CXCR4, prevents the accumulation of leukemic cells in the bone marrow, which promotes the efficacy of .... It also contributes to the formation of a pro-tumor microenvironment and can confer resistance to chemotherapy.In this study we developed a derivative of theCXCR4 peptide antagonist, T140-2D, that can be labeled easily with the PET isotope copper-64, and thereby enable ...
CXCR4 peptide antagonists are designed to bind to the CXCR4 receptor and prevent its activation by CXCL12. Unlike small molecule antagonists, peptide-based inhibitors can offer distinct advantages in terms of specificity and mechanism of action.
* Specific Peptide Inhibitors: Compounds like LY2510924 are potent and selective peptide antagonists that have demonstrated efficacy in preclinical models of various cancers, including renal cell carcinoma, lung cancer, colon cancer, and breast cancer. These peptides work by directly blocking the ligand-binding site of CXCR4作者：O Zirafi·2015·被引用次数：120—EPI-X4 forms an unusual lasso-like structure andantagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses ....
* Endogenous Antagonists: Research has also identified endogenous peptides, such as EPI-X4, which possess CXCR4 antagonist properties.作者：MD Galsky·2014·被引用次数：133—This article reports the results of a phase I study designed to evaluate the safety and tolerability of the CXC motif receptor 4 (CXCR4) inhibitor LY2510924 in ... These molecules can form unique lasso-like structures and effectively antagonize CXCL12-induced tumor cell migration, mobilize stem cells, and suppress inflammatory responses, offering a natural approach to modulating CXCR4 signaling.
* Modified Variants: Efforts are underway to improve the properties of existing peptide antagonists through N-terminal modifications or other structural alterationsSmall molecule and peptide CXCR4 antagonists. A patent .... These modifications aim to enhance their stability, potency, and delivery, thereby improving their therapeutic potential.
The ability of CXCR4 peptide antagonists to interfere with tumor growth and metastasis, as well as to mobilize stem cells, has led to their investigation in several therapeutic areas.
* Oncology: By inhibiting the CXCR4/CXCL12 axis, these antagonists can disrupt tumor cell homing to specific organs, reduce tumor angiogenesis, and enhance the efficacy of other cancer therapies. Preclinical studies have shown that CXCR4 peptide antagonists can slow tumor growth and inhibit metastasis in various cancer types.
* Stem Cell Mobilization: Similar to small molecule antagonists like AMD3100 (Plerixafor), peptide antagonists can be used to mobilize hematopoietic stem cells from the bone marrow into the peripheral blood. This is a critical step for autologous and allogeneic stem cell transplantation, used in the treatment of hematological malignancies and other conditions.
* Imaging: Modified CXCR4 peptide antagonists, such as those labeled with positron emission tomography (PET) isotopes like copper-64, are being developed for molecular imaging. These agents can help visualize CXCR4 expression in tumors, aiding in diagnosis, staging, and treatment monitoring.
Despite the significant promise of CXCR4 peptide antagonists, several challenges remainDefinition of CXCR4 peptide antagonist LY2510924. Ensuring optimal pharmacokinetic properties, such as bioavailability and half-life, is crucial for effective in vivo application.Small molecule and peptide CXCR4 antagonists. A patent ... Furthermore, understanding potential off-target effects and developing strategies to mitigate antagonist tolerance are important areas of researchAn inhibitor of CXC chemokine receptor 4 (CXCR4), with potential antineoplastic activity. Upon subcutaneous administration,CXCR4 inhibitor LY2510924binds ....
The development of biased antagonism for CXCR4 is an emerging strategy that aims to selectively activate certain downstream signaling pathways while blocking others, potentially leading to more targeted therapeutic benefits with fewer side effects.作者：H Guo·2017·被引用次数：39—Peptide LY2510924 is a potent and selective CXCR4 antagonistfor inhibiting renal cell carcinoma, lung, colon cancer and breast cancer that ... Continued research into novel peptide designs, improved delivery systems, and combination therapies will likely expand the clinical utility of CXCR4 peptide antagonists in treating cancer, inflammatory diseases, and in regenerative medicine applications作者：O Zirafi·2015·被引用次数：120—EPI-X4 forms an unusual lasso-like structure andantagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses ....
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