C-X-C motif chemokine receptor 1 and 2 (CXCR1/CXCR2)

The C-X-C motif chemokine receptor 1 and 2 (CXCR1/CXCR2) signaling axis is a critical pathway in the innate immune system, primarily responsible for the recruitment and activation of neutrophils to sites of inflammation (UniProt P25024, P25025). These G protein-coupled receptors are activated by ELR-positive chemokines, most notably interleukin-8 (CXCL8), which triggers downstream signaling cascades like PI3K/Akt and MAPK (PMID: 31435456). In the context of oncology, the CXCR1/CXCR2 axis is frequently hijacked by tumors to promote angiogenesis, facilitate the epithelial-mesenchymal transition, and recruit myeloid-derived suppressor cells to the tumor microenvironment (PMID: 28844403, PMID: 27070089). Consequently, this axis has become a significant therapeutic target for both inflammatory diseases and various cancers. Small molecule inhibitors and antagonists, such as reparixin and SX-682, are being developed to disrupt this signaling, aiming to reduce tumor progression and alleviate chronic inflammatory conditions (Dompé Pharmaceuticals, Syntrix Biosystems). However, therapeutic intervention must be carefully managed due to the risk of neutropenia and impaired host defense against pathogens.

Other names

IL8RAIL8RBCD181CD182Interleukin-8 receptor type AInterleukin-8 receptor type BCXCL8 receptorsHigh affinity interleukin-8 receptor AHigh affinity interleukin-8 receptor B

Small molecule antagonism or allosteric inhibition of CXCR1 and CXCR2 receptors to block chemokine-mediated signaling and cellular recruitment.