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 viruss 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.
Plerixafor (INN and USAN, trade name Mozobil) is an immunostimulant used to mobilize hematopoietic stem cells in cancer patients into the bloodstream. The stem cells are then extracted from the blood and transplanted back to the patient. The drug was developed by AnorMED, which was subsequently bought by Genzyme. Medical uses
Peripheral blood stem cell mobilization, which is important as a source of hematopoietic stem cells for transplantation, is generally performed using granulocyte colony-stimulating factor (G-CSF), but is ineffective in around 15 to 20% of patients. Combination of G-CSF with plerixafor increases the percentage of persons that respond to the therapy and produce enough stem cells for transplantation. The drug is approved for patients with lymphoma and multiple myeloma.Phase 2 clinical trials started in 2021 exploring the combination of plerixafor and MGTA-145, a CXCL2 ligand. Contraindications
Pregnancy and lactation
Studies in pregnant animals have shown teratogenic effects. Plerixafor is therefore contraindicated in pregnant women except in critical cases. Fertile women are required to use contraception. It is not known whether the drug is secreted into the breast milk. Breast feeding should be discontinued during therapy. Adverse effects
Nausea, diarrhea and local reactions were observed in over 10% of patients. Other problems with digestion and general symptoms like dizziness, headache, and muscular pain are also relatively common; they were found in more than 1% of patients. Allergies occur in less than 1% of cases.