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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
AMD3100: CXCR4 antagonist and rapid stem cell-mobilizing agent
Amanda F Cashen1, Bruno Nervi, John DiPersio
1Washington University School of Medicine, Division of Oncology, 660 South Euclid Avenue, Campus Box 8007, St Louis, MO 63110, USA. acashen@im.wustl.edu
As hematopoietic stem cells collected from peripheral blood are increasingly used for autologous and allogeneic stem cell transplantation, new approaches for the mobilization of stem cells are needed. These should have the goal of improving stem cell collection and reducing the duration and toxicity of the mobilization process. AMD3100, a specific inhibitor of CXCR4, one of the key molecules that tethers hematopoietic stem cells to the bone marrow microenvironment, is a promising new agent currently in clinical development for autologous and allogeneic stem cell mobilization. Early clinical trials have demonstrated that AMD3100 rapidly mobilizes stem cells to the peripheral blood, with minimal side effects. In Phase II trials, mobilization with the combination of AMD3100 and granulocyte colony-stimulating factor (G-CSF) results in the collection of more progenitor cells than G-CSF alone.
As hematopoietic stem cells collected from peripheral blood are increasingly used for autologous and allogeneic stem cell transplantation, new approaches for the mobilization of stem cells are needed. These should have the goal of improving stem cell collection and reducing the duration and toxicity of the mobilization process. AMD3100, a specific inhibitor of CXCR4, one of the key molecules that tethers hematopoietic stem cells to the bone marrow microenvironment, is a promising new agent currently in clinical development for autologous and allogeneic stem cell mobilization. Early clinical trials have demonstrated that AMD3100 rapidly mobilizes stem cells to the peripheral blood, with minimal side effects. In Phase II trials, mobilization with the combination of AMD3100 and granulocyte colony-stimulating factor (G-CSF) results in the collection of more progenitor cells than G-CSF alone.
