CXCR4 Receptor
A chemokine receptor found on stem cells, immune cells, and cancer cells. CXCR4 plays a critical role in retaining haematopoietic stem cells in bone marrow. Motixafortide is a CXCR4 antagonist that mobilises stem cells into the blood for collection in transplant preparation.
Technical Context
CXCR4 (CD184) is a 7-transmembrane GPCR (Gαi-coupled → inhibits adenylyl cyclase, activates PI3K, mobilises calcium) with a single natural ligand: CXCL12/SDF-1 (68 amino acids). CXCR4 is expressed on: HSCs and haematopoietic progenitors (marrow retention), T cells, B cells, monocytes (immune trafficking), endothelial progenitor cells (vascular repair), neurons (brain development), and many cancer types (promoting metastasis to CXCL12-rich tissues — bone marrow, liver, lung). Motixafortide (BL-8040) is a cyclic 14-amino-acid peptide (with a 4-fluorobenzoyl modification) that antagonises CXCR4 with high affinity. Approved for HSC mobilisation in myeloma, it is also investigated for: pancreatic cancer (disrupting tumour-stroma interactions), AML (mobilising leukaemia stem cells from protective marrow niches to increase chemotherapy sensitivity), and enhancing checkpoint immunotherapy (increasing tumour T cell infiltration by disrupting CXCR4-mediated immune exclusion).