vivo effect of plerixafor with regard to ubiquitin, the alternative endogenous ligand of CXCR4, is unknown. Plerixafor has been found to be a strong inducer of mobilization of hematopoietic stem cells from the bone marrow to the bloodstream as peripheral blood stem cells. Additionally, plerixafor inhibits CD20 expression on B cells by interfering with CXCR4/SDF1 axis that regulates its expression. Pharmacokinetics Following subcutaneous injection, plerixafor is absorbed quickly and peak concentrations are reached after 30 to 60 minutes. Up to 58% are bound to plasma proteins, the rest mostly resides in extravascular compartments. The drug is not metabolized in significant amounts; no interaction with the cytochrome P450 enzymes or P-glycoproteins has been found. Plasma half life is 3 to 5 hours. Plerixafor is excreted via the kidneys, with 70% of the drug being excreted within 24 hours. Chemistry Plerixafor is a macrocyclic compound and a bicyclam derivative, the cyclam rings being linked at the amine nitrogen atoms by a 1,4-xylyl spacer. It is a base; all eight nitrogen atoms accept protons readily. The two macrocyclic rings form chelate complexes with bivalent metal ions, especially zinc, copper and nickel, as well as cobalt and rhodium. The biologically active form of plerixafor is its zinc complex. Synthesis Three of the four nitrogen atoms of the macrocycle cyclam... (1,4,8,11-tetraazacyclotetradecane) are protected with tosyl groups. The product is treated with 1,4-bis(brommethyl)benzene and potassium carbonate in acetonitrile. After cleaving of the tosyl groups with hydrobromic acid, plerixafor octahydrobromide is obtained. History The molecule was first synthesised in 1987 to carry out basic studies on the redox chemistry of dimetallic coordination compounds. Then, it was serendipitously discovered by another chemist that such a molecule could have a potential use in the treatment of HIV because of its role in the blocking of CXCR4, a chemokine receptor which acts as a co-receptor for certain strains of HIV (along with the virus's main cellular receptor, CD4). Development of this indication was terminated because of lacking oral availability and cardiac disturbances. Further studies led to the new indication for cancer patients. Society and culture Plerixafor has orphan drug status in the United States and European Union for the mobilization of hematopoietic stem cells. It was approved by the U.S. Food and Drug Administration (FDA) for this indication on 15 December 2008. In the European Union, the drug was approved after a positive Committee for Medicinal Products for Human Use