In recent years, the chemokine receptor CXCR4 has been shown to be
implemented in the mobilization of progenitor cells from the bone marrow. This
finding has prompted a search for CXCR4 antagonists acting as stem cell mobilizing
agents. In accordance, it is important to look into the molecular pharmacology
of well-known CXCR4 antagonists in order to augment the potency and affinity and
to increase the specificity of future CXCR4-targeting compounds. In this chapter,
binding modes of CXCR4 antagonists that have been shown to mobilize stem cells
are discussed. In addition, comparisons between results obtained from structure–
function studies and findings from newly released crystal structures are drawn.