# Plerixafor
**Plerixafor** (trade name Mozobil; originally AMD3100) is a small-molecule antagonist of the CXCR4 chemokine receptor used as a hematopoietic stem cell mobilizer, in combination with filgrastim, to move hematopoietic stem cells into the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma or multiple myeloma.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) It was originally developed as an anti-HIV drug and reached its current use through a chain of unexpected clinical observations.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC4947283/)
| Key fact | Detail |
|---|---|
| Mechanism | Inhibits the CXCR4 chemokine receptor and blocks binding of its ligand, stromal cell-derived factor-1α (SDF-1α)[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) |
| US approval | Approved by the FDA for HSC mobilization on December 15, 2008[3](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/plerixafor) |
| Indication | With filgrastim, to mobilize HSCs for autologous transplantation in non-Hodgkin's lymphoma or multiple myeloma[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) |
| Dose | 0.24 mg/kg subcutaneously (20 mg fixed dose for patients ≤83 kg), about 11 hours before apheresis, for up to 4 consecutive days[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) |
| Renal dosing | Creatinine clearance ≤50 mL/min: dose reduced by one-third to 0.16 mg/kg, not exceeding 27 mg/day[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) |
| Common adverse reactions | Diarrhea (37%), nausea (34%), injection site reactions (34%), fatigue (27%), headache (22%) in the randomized trials[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) |
| Elimination | Not metabolized by the CYP system; about 70% of the dose is excreted in urine within 24 hours with normal renal function[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4093299/) |
## Mechanism
CXCR4 is the receptor for stromal cell-derived factor-1α (SDF-1α, also called CXCL12), a chemokine that retains hematopoietic stem and progenitor cells in the bone marrow. By blocking the binding of SDF-1α to CXCR4, plerixafor releases these cells into the peripheral blood, where they can be collected by apheresis.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC4947283/) The same receptor serves as a co-receptor for T-lymphotropic HIV strains entering host T cells, which is why the compound was first pursued as an antiviral agent.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC3065558/)
## Discovery history
The compound's path to approval began with an impurity. A bicyclam designated JM1657 (JM for [Johnson Matthey](https://www.edgepedia.org/johnson-matthey)) was identified as an impurity in a commercial (mono)cyclam preparation being evaluated for inhibition of HIV replication. A successor with the two cyclam rings tethered by a propyl bridge, JM2763, proved a potent and selective inhibitor of both HIV-1 and HIV-2 replication. Replacing the propyl bridge with an aromatic bridge produced JM3100, renamed AMD3100 when AnorMED, a spin-off of Johnson Matthey, took over development; this change brought a dramatic increase in anti-HIV potency. AMD3100 was later found to be a specific inhibitor of CXCR4.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC6379795/)
**The serendipitous turn.** As a prerequisite to clinical development against HIV, Craig Hendrix and colleagues at [Johns Hopkins University](https://www.edgepedia.org/johns-hopkins-university), with AnorMED investigators, examined AMD3100's safety in human volunteers and found an increase in white blood cell counts peaking about 8 to 10 hours after subcutaneous injection. On closer inspection these cells included CD34-positive hematopoietic stem cells, which normally make up less than 0.05% of white blood cells.[11](https://www.ema.europa.eu/en/documents/assessment-report/mozobil-epar-public-assessment-report_en.pdf) Broxmeyer and colleagues then provided the first proof of principle that AMD3100 could mobilize hematopoietic stem cells, and the concept of the drug as a stem cell mobilizer was born.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC6379795/) Genzyme Corporation completed its acquisition of AnorMED in 2006, and two phase III, multicenter, double-blind, randomized, placebo-controlled studies provided the evidence for FDA approval of plerixafor in December 2008.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC4947283/) • [3](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/plerixafor)
## Clinical use
The approved regimen pairs plerixafor with filgrastim (G-CSF). Patients receive filgrastim 10 mcg/kg each morning for 4 days before the first evening dose of plerixafor, which is given subcutaneously approximately 11 hours before apheresis begins, and dosing of both drugs continues daily until a sufficient CD34+ cell count is achieved, for a maximum of 4 consecutive days of plerixafor.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) • [4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4093299/) Peripheral CD34+ cell counts peak 10 to 14 hours after administration, which is why the drug is generally dosed in the evening before apheresis.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4093299/)
**Dose adjustments.** Because plerixafor is primarily eliminated by the kidneys, patients with moderate or severe renal impairment (estimated creatinine clearance ≤50 mL/min) receive a one-third dose reduction to 0.16 mg/kg, capped at 27 mg/day; the cap reflects increasing exposure with increasing body weight on mg/kg dosing.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) In a pharmacokinetic study, mean [AUC](https://www.edgepedia.org/area-under-the-curve-pharmacokinetics) over 24 hours was 7%, 32%, and 39% higher than in healthy subjects for mild, moderate, and severe renal impairment respectively, and renal impairment had no effect on peak concentration.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf)
**Safety profile.** In the two randomized trials (301 patients on plerixafor plus filgrastim, 292 on placebo plus filgrastim), the reactions occurring in at least 10% of patients and more often with plerixafor were diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, and vomiting; no grade 4 events were reported for these reactions.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) • [4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4093299/) The label carries warnings for anaphylactic shock and serious hypersensitivity reactions, leukocytosis and thrombocytopenia, splenic enlargement and rupture, and embryo-fetal toxicity.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) Because the drug can mobilize leukemic cells and contaminate the apheresis product, it is not intended for stem cell mobilization in patients with leukemia.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf) Its low interaction potential follows from its metabolism: it is not metabolized by the CYP system and does not inhibit or induce any CYP isoenzymes.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4093299/)
## Chemistry
Plerixafor is a bicyclam: two cyclam rings (macrocyclic tetraamines) connected by a 1,4-phenylenebis(methylene) linker. Crucial aspartic acid residues at positions 171, 182, 193, and 262 of CXCR4 mediate the interaction with the compound.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4459229/) • [8](https://pmc.ncbi.nlm.nih.gov/articles/PMC3776399/) Guided by AMD3100 as a prototype, related CXCR4 antagonists were synthesized, and AMD070 was identified as a potent, orally bioavailable CXCR4 antagonist that inhibits HIV infectivity at an EC50 of 1 to 10 nM.[9](https://www.sciencedirect.com/science/article/pii/S0006295208009039)
## Current position
A 2025 update of the American Society of Clinical Oncology guideline on white blood cell growth factors recommends, for peripheral blood stem-cell mobilization, a CXCR4 inhibitor, either motixafortide or plerixafor, in combination with G-CSF, since both agents are associated with higher rates of successful collection compared with G-CSF alone.[10](https://ascopubs.org/doi/full/10.1200/JCO-25-02938) The rapid kinetics of mobilization with plerixafor have also prompted investigation of additional clinical uses beyond the approved indication, including studies in leukemia and solid tumors.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC4947283/)
## References
1. [MOZOBIL (plerixafor) injection, Full Prescribing Information, FDA (revised 9/2023)](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022311s023lbl.pdf)
2. [Effectiveness of AMD3100 in treatment of leukemia and solid tumors: from original discovery to use in current clinical practice, Experimental Hematology & Oncology (2016)](https://pmc.ncbi.nlm.nih.gov/articles/PMC4947283/)
3. [Plerixafor – an overview, ScienceDirect Topics](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/plerixafor)
4. [Plerixafor, Annals of Pharmacotherapy via PMC (2011)](https://pmc.ncbi.nlm.nih.gov/articles/PMC4093299/)
5. [Plerixafor for autologous CD34+ cell mobilization, PMC (2009)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3065558/)
6. [Mozobil (Plerixafor, AMD3100), 10 years after its approval by the US FDA, PMC (2018)](https://pmc.ncbi.nlm.nih.gov/articles/PMC6379795/)
7. [AMD3100/CXCR4 Inhibitor, PMC (2013)](https://pmc.ncbi.nlm.nih.gov/articles/PMC4459229/)
8. [Physiology and Pharmacology of Plerixafor, PMC (2012)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3776399/)
9. [The AMD3100 story: the path to the discovery of a stem cell mobilizer (Mozobil), Biochemical Pharmacology](https://www.sciencedirect.com/science/article/pii/S0006295208009039)
10. [WBC Growth Factors: ASCO Guideline Update, Journal of Clinical Oncology (2025)](https://ascopubs.org/doi/full/10.1200/JCO-25-02938)
11. [Mozobil Epar Public Assessment Report En.pdf, ema.europa.eu](https://www.ema.europa.eu/en/documents/assessment-report/mozobil-epar-public-assessment-report_en.pdf)
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*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Organic substances › Amines and nitrogen functional groups › Aliphatic amines and polyamines › Diamines and polyamines*
*Initially written Oct 15, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license