CXCR4 antagonists

Abstract

All major pharmaceutical and several Biotech companies have invested over many years significant resources into the field of modulation of chemokines and their receptors for discovery and development novel drugs. Despite these efforts, the outcome has not fulfilled up to now the expectations. Only two compounds have been approved by regulatory authorities and are being marketed: the CCR5 antagonist maraviroc (Celsentri®) acting as HIV entry inhibitor was approved in 2007, followed shortly afterward by the CXCR4 antagonist plerixafor or AMD3100 (Mozobil®): plerixafor was approved in December 2008 by the FDA for subcutaneous injection in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). EMA approval followed in August 2009 for Europe to enhance mobilization of stem cells to the bloodstream (in combination with G-CSF) for collection and subsequent autologous transplantation in patients with lymphoma and multiple myeloma whose cells mobilize poorly.