Molecular pharmacology of CXCR4 inhibition

Abstract

In recent years, the chemokine receptor CXCR4 has been shown to be implemented in the mobilization of progenitor cells from the bone marrow. This fi nding 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 affi nity and to increase the specifi city 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 fi ndings from newly released crystal structures are drawn.