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C-X-C motif chemokine ligand 2 (CXCL2), also known as Macrophage Inflammatory Protein 2-alpha (MIP2-alpha) or Growth-Regulated Protein beta (GRO-beta), is a small proinflammatory cytokine belonging to the CXC chemokine family [1, 2, 9]. It is primarily produced by activated monocytes, neutrophils, and macrophages at sites of injury or infection [9, 14]. CXCL2 functions as a potent chemoattractant for neutrophils by binding to and activating the G protein-coupled receptor CXCR2, thereby facilitating the recruitment of immune cells to inflammatory sites [1, 2, 18]. In addition to its role in acute inflammation, CXCL2 is a critical component of the tumor microenvironment, where it promotes angiogenesis, tumor cell proliferation, and the recruitment of myeloid-derived suppressor cells (MDSCs) that contribute to immune evasion and metastasis [1, 2, 15]. In clinical research, CXCL2 is recognized as a significant prognostic biomarker for several cancers, including gastric, colorectal, and hepatocellular carcinomas, where its expression levels often correlate with disease progression and patient survival [11, 15, 16]. Therapeutic strategies targeting the CXCL2/CXCR2 axis focus on disrupting this signaling pathway to treat inflammatory diseases and inhibit tumor growth [2, 7]. Current pharmacological approaches primarily involve small-molecule CXCR2 antagonists, such as Navarixin and AZD5069, which have been evaluated in clinical trials for conditions like COPD and various solid tumors [5, 6, 8].
CXCR2 antagonism, CXCR1/2 dual antagonism, ligand neutralization, and CXCR2 agonism (via recombinant protein).
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