CXCR4/CXCL12 axis: "old" pathway as "novel" target for anti-inflammatory drug discovery
Liuxin Lu1,2, Junjie Li1,2, Xiaoying Jiang1,2
1Department of Medicinal Chemistry, School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Abstract:
Inflammation is the body's defense response to exogenous or endogenous stimuli, involving complex regulatory mechanisms. Discovering anti-inflammatory drugs with both effectiveness and long-term use safety is still the direction of researchers' efforts. The inflammatory pathway was initially identified to be involved in tumor metastasis and HIV infection. However, research in recent years has proved that the CXC chemokine receptor type 4 (CXCR4)/CXC motif chemokine ligand 12 (CXCL12) axis plays a critical role in the upstream of the inflammatory pathway due to its chemotaxis to inflammatory cells. Blocking the chemotaxis of inflammatory cells by CXCL12 at the inflammatory site may block and alleviate the inflammatory response. Therefore, developing CXCR4 antagonists has become a novel strategy for anti-inflammatory therapy. This review aimed to systematically summarize and analyze the mechanisms of action of the CXCR4/CXCL12 axis in more than 20 inflammatory diseases, highlighting its crucial role in inflammation. Additionally, the anti-inflammatory activities of CXCR4 antagonists were discussed. The findings might help generate new perspectives for developing anti-inflammatory drugs targeting the CXCR4/CXCL12 axis.
Insights
Researchers are exploring the CXC chemokine receptor type 4 (CXCR4)/CXC motif chemokine ligand 12 (CXCL12) axis as a novel target for anti-inflammatory drugs. Blocking this axis shows promise in alleviating inflammatory responses across various diseases.
Area of Science:
- Immunology
- Pharmacology
- Molecular Biology
Background:
- Inflammation is a critical biological response to stimuli, necessitating safe and effective anti-inflammatory treatments.
- The CXC chemokine receptor type 4 (CXCR4)/CXC motif chemokine ligand 12 (CXCL12) axis is increasingly recognized for its upstream role in inflammatory pathways.
- This axis influences inflammatory cell chemotaxis, impacting disease progression.
Purpose of the Study:
- To systematically review the role of the CXCR4/CXCL12 axis in over 20 inflammatory diseases.
- To analyze the mechanisms by which this axis contributes to inflammation.
- To discuss the anti-inflammatory potential of CXCR4 antagonists.
Main Methods:
- Literature review and systematic analysis of existing research on the CXCR4/CXCL12 axis in inflammation.
- Examination of preclinical and clinical data regarding CXCR4 antagonists.
- Synthesis of findings to elucidate the axis's role and therapeutic implications.
Main Results:
- The CXCR4/CXCL12 axis is a key regulator of inflammatory cell migration in numerous inflammatory conditions.
- Blocking the CXCR4/CXCL12 interaction demonstrates significant potential for mitigating inflammatory processes.
- CXCR4 antagonists represent a promising therapeutic strategy for managing inflammatory diseases.
Conclusions:
- The CXCR4/CXCL12 axis is a critical mediator in the pathogenesis of diverse inflammatory diseases.
- Targeting the CXCR4/CXCL12 axis offers a novel and effective approach for developing next-generation anti-inflammatory therapies.
- Further research into CXCR4 antagonists could lead to improved treatments for patients suffering from inflammatory conditions.
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