CXCR4 Antibodies

Structure of CXCR4

CXCR4 is a G protein-coupled receptor (GPCR) with a molecular weight of approximately 48 kDa. There are minor differences in its molecular weight among different species, mainly due to conserved variations in amino acid sequences.

CXCR4 is composed of 352 amino acids and features typical GPCR structural characteristics, including 7 transmembrane α -helicles (TM1-TM7), an extracellular N-terminal domain, and an intracellular C-terminal tail. Its ligand binding pocket is located in the transmembrane region, and key residues (such as Asp171, Asp262) bind to CXCL12 (SDF-1) and trigger downstream signals. The intracellular region of the receptor contains the DRY motif (Asp-Arg-Tyr), which is responsible for G protein coupling, while the C-terminal is rich in serine/threonine and participates in receptor regulation and internalization. The secondary structure of CXCR4 is mainly an α -helix. Its three-dimensional conformation undergoes conformational changes when binding to CXCL12 or HIV gp120, affecting immune function and the mechanism of viral invasion.

Fig. 1 Targeting CXCR4.¹

Key structural properties of CXCR4:

• 7-time transmembrane helical structure
• Conservative DRY motif (Asp-Arg-Tyr)
• Cysteine disulfide bond (Cys28-Cys274)
• N-terminal acidic residue cluster (Asp14/Asp15)
• C-terminal phosphorylation site (Ser324/Ser325)

Functions of CXCR4

The core function of CXCR4 is to mediate cell migration and signal transduction, and it also plays a key role in pathological processes.

Its functional diversity makes CXCR4 a key target for cancer immunotherapy, anti-HIV drugs and stem cell therapy.

Applications of CXCR4 and CXCR4 Antibody in Literature

1. Peng, Sheng-Bin, et al. "Inhibition of CXCR4 by LY2624587, a fully humanized anti-CXCR4 antibody induces apoptosis of hematologic malignancies." PloS one 11.3 (2016): e0150585. https://doi.org/10.1371/journal.pone.0150585

In this study, a humanized anti-CXCR4 monoclonal antibody LY2624587 was developed, which can efficiently block the binding of SDF-1/CXCR4 (IC50 0.26 nM), inhibit tumor cell migration (IC50 0.26-3.7 nM), and induce receptor internalization. This antibody significantly induces apoptosis, inhibits tumor growth and prolongs survival in hematological tumor models by suppressing the MAPK/AKT signaling pathway, demonstrating therapeutic potential.

2. Costa, Maria José, et al. "Optimal design, anti-tumour efficacy and tolerability of anti-CXCR4 antibody drug conjugates." Scientific Reports 9.1 (2019): 2443.https://doi.org/10.1038/s41598-019-38745-x

This study designed the first antibody-drug conjugate (ADC) targeting CXCR4. By optimizing the link-payload combination, drug-antibody ratio (DAR=4), and low-affinity antibodies, it effectively cleared cancer cells as a single agent in hematological malignancies models while reducing toxicity to normal CXCR4+ tissues (such as hematopoietic stem cells). Provide new strategies for the development of ADCs with broad-spectrum target expression.

3. Cancilla, Daniel, Michael P. Rettig, and John F. DiPersio. "Targeting CXCR4 in AML and all." Frontiers in oncology 10 (2020): 1672. https://doi.org/10.3389/fonc.2020.01672

This study indicates that CXCR4 is highly expressed in AML and ALL, interacting with CXCL12 to promote the homing of leukemia cells to the bone marrow and enhance survival, leading to a poor prognosis. Currently, small molecule inhibitors, antibodies and antibody-drug conjugates (ADCs) targeting CXCR4 are under development, aiming to block the CXCR4/CXCL12 axis, overcome microenvironment-mediated chemotherapy resistance, and provide new strategies for leukemia treatment.

4. Piloto, Ana Margarida, et al. "Plastic antibodies tailored on quantum dots for an optical detection of myoglobin down to the femtomolar range." Scientific reports 8.1 (2018): 4944. https://doi.org/10.1371/journal.pone.0004069

This study developed a novel rabbit monoclonal antibody, UMB-2, which specifically recognizes the surface receptor of CXCR4 cells. Experiments have confirmed that it can effectively detect CXCR4 in transfected cells and normal mouse tissues, and show membrane localization staining in paraffin-embedded tumor tissues, which is superior to commonly used antibodies such as 12G5, providing a reliable tool for clinical pathological assessment of CXCR4 expression.

5. Portella, Luigi, et al. "Preclinical development of a novel class of CXCR4 antagonist impairing solid tumors growth and metastases." PloS one 8.9 (2013): e74548.https://doi.org/10.1371/journal.pone.0074548

In this study, a novel cyclic peptide CXCR4 antagonist was developed based on the key amino acid motif of CXCL12. The preferred peptide R/S/I can effectively inhibit the binding of 12G5 antibody to CXCR4 (IC50 up to 10nM), significantly reduce lung metastasis of melanoma (B16-CXCR4 model) and subcutaneous growth of renal cancer (SN12C model), providing a new strategy for anti-cancer treatment.

Creative Biolabs: CXCR4 Antibodies for Research

Creative Biolabs specializes in the production of high-quality CXCR4 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom CXCR4 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our CXCR4 antibodies, custom preparations, or technical support, contact us at email.