C-X-C chemokine receptor type 2–Angiotensin II type 1 receptor heteromer (CXCR2–AT1R heteromer)

The C-X-C chemokine receptor type 2–Angiotensin II type 1 receptor (CXCR2–AT1R) heteromer is a macromolecular complex formed by the physical and functional association of the Interleukin-8 receptor beta (CXCR2) and the Angiotensin II type 1 receptor (AT1R). This G protein-coupled receptor (GPCR) heteromer facilitates significant cross-talk between the chemokine system and the renin-angiotensin system, often resulting in the transactivation of CXCR2 upon AT1R stimulation. In chronic inflammatory conditions such as Chronic Obstructive Pulmonary Disease (COPD), the formation of this heteromer is linked to the abnormal recruitment of neutrophils and subsequent lung tissue damage. Therapeutic strategies targeting this complex, such as the drug candidate DMX-700, utilize simultaneous inhibition of both receptor components to achieve a synergistic anti-inflammatory effect that is more potent than monotherapy. By blocking the heteromer-specific signaling pathways, these treatments aim to reduce mucus production, inflammation, and progressive lung injury. The identification of such heteromers provides a novel pharmacological target for diseases where traditional single-receptor antagonists have shown limited clinical efficacy.

Other names

IL-8Rβ–AT1R heteromerCXCR2–AGTR1 heteromerInterleukin-8 receptor type B–Angiotensin II receptor type 1 heteromerCXC chemokine receptor 2–Angiotensin II type 1 receptor heteromer

Simultaneous inhibition of both CXCR2 and AT1R within the heteromer complex to prevent receptor transactivation and synergistically abolish signaling involved in neutrophil recruitment and tissue inflammation.