Atypical chemokine receptor 3 (ACKR3) mRNA (ACKR3)

Atypical chemokine receptor 3 (ACKR3), formerly known as CXCR7, is a non-canonical G protein-coupled receptor that primarily functions as a high-affinity scavenger for the chemokines CXCL12 (SDF-1) and CXCL11 (I-TAC) [1, 3]. Unlike classical chemokine receptors, ACKR3 does not activate G-protein signaling pathways but instead recruits beta-arrestins to internalize and degrade its ligands, thereby regulating chemokine availability in the extracellular environment [1, 4]. This scavenging activity is essential for establishing chemokine gradients that guide cell migration during development, particularly in the cardiovascular and nervous systems [2, 4]. In pathological conditions, ACKR3 is frequently upregulated in various cancers, where it promotes tumor cell survival, proliferation, and metastasis by modulating the CXCR4/CXCL12 signaling axis [4]. Therapeutic strategies targeting ACKR3 include small molecule antagonists and monoclonal antibodies designed to disrupt its scavenging function or its interaction with CXCR4 [5]. Additionally, targeting ACKR3 mRNA via RNA-based therapeutics is an emerging area of interest to downregulate receptor expression in disease states [4].

Other names

CXCR7CXC chemokine receptor type 7Chemokine orphan receptor 1CMKOR1RDC1G-protein coupled receptor 159GPR159

Antagonism of the receptor to prevent the scavenging of CXCL12 and CXCL11, thereby modulating the CXCR4/CXCL12 signaling axis and inhibiting beta-arrestin-mediated signaling pathways [3, 4].