A CXCR4 antagonist is a substance which blocks the

CXCR4 C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the ''CXCR4'' gene. The protein is a CXC chemokine receptor. Function CXCR-4 is an alpha-chemokin ...

receptor and prevent its activation. Blocking the receptor stops the receptor's

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

CXCL12 The stromal cell-derived factor 1 (SDF-1), also known as C-X-C motif chemokine 12 (CXCL12), is a chemokine protein that in humans is encoded by the ''CXCL12'' gene on chromosome 10. It is ubiquitously expressed in many tissues and cell types. Str ...

, from binding which prevents downstream effects. CXCR4 antagonists are especially important for hindering cancer progression because one of the downstream effects initiated by CXCR4 receptor activation is cell movement which helps the spread of cancer, known as

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then ...

. The CXCR4 receptor has been targeted by antagonistic substances since being identified as a co-receptor in

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

and assisting the development of cancer. Macrocyclic ligands have been utilised as CXCR4 antagonists.

Plerixafor Plerixafor ( INN and USAN, trade name Mozobil) is an immunostimulant used to mobilize hematopoietic stem cells in cancer patients into the bloodstream. The stem cells are then extracted from the blood and transplanted back to the patient. The dr ...

is an example of a CXCR4 antagonist, and has approvals (e.g. US FDA 2008) for clinical use (to mobilize hematopoietic stem cells). BL-8040 is a CXCR4 antagonist that has undergone clinical trials (e.g. in various

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

s), with one planned for pancreatic cancer (in combination with

pembrolizumab Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast canc ...

). Previously called BKT140, it is a synthetic cyclic 14-residue peptide with an aromatic ring. In a 2018 mouse tumor model study, BL-8040 treatment enhanced anti-tumor immune response potentially by increasing the CD8+ T-cells in the

tumor microenvironment The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are ...

References

{{Cytokine receptor modulators Cancer treatments Receptor antagonists