C-X-C chemokine receptor type 4 (CXCR4) (CXCR4)

Human CXCR4 (C-X-C chemokine receptor type 4) is a Class A G protein-coupled receptor (GPCR) that specifically binds the chemokine CXCL12 (also known as stromal cell-derived factor-1 or SDF-1) [1, 6]. It plays a fundamental role in the homeostatic regulation of hematopoietic stem cell (HSC) trafficking, ensuring their retention and homing within the bone marrow niche [6, 8]. Beyond hematopoiesis, CXCR4 is critical for embryonic development, particularly in the formation of the cardiovascular and nervous systems [1, 16]. In pathological contexts, CXCR4 is a well-known coreceptor for the entry of X4-tropic HIV-1 strains into T cells [4, 10]. It is also frequently overexpressed in numerous cancers, where the CXCR4/CXCL12 axis promotes tumor cell survival, proliferation, angiogenesis, and organ-specific metastasis [7, 17]. Therapeutic targeting of CXCR4 primarily involves antagonists like Plerixafor, which is used to mobilize HSCs for transplantation, and Mavorixafor, recently approved for treating WHIM syndrome [8, 17]. Ongoing research explores CXCR4 inhibition as a strategy to sensitize cancer cells to chemotherapy and to prevent metastatic spread [12, 15].

Other names

CD184FusinLESTRNPY3RWHIMHM89FB22

CXCR4 antagonists block the binding of the ligand CXCL12, inhibiting downstream signaling pathways like PI3K/Akt and MAPK [6, 7]. This blockade mobilizes hematopoietic stem cells from the bone marrow into the peripheral blood [8]. In HIV, CXCR4 antagonists prevent viral gp120 interaction, blocking entry [10]. In oncology, they disrupt tumor-stromal interactions and inhibit metastasis [17].