Plerixafor

Identification

Summary

Plerixafor is a selective chemokine receptor (CXCR4) antagonist used with filgrastim to mobilize hematopoietic stem cells to the peripheral blood for collection and autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM).

Brand Names
Mozobil
Generic Name
Plerixafor
DrugBank Accession Number
DB06809
Background

Plerixafor is a hematopoietic stem cell mobilizer. It is used to stimulate the release of stem cells from the bone marrow into the blood in patients with non-Hodgkin lymphoma and multiple myeloma for the purpose of stimulating the immune system. These stem cells are then collected and used in autologous stem cell transplantation to replace blood-forming cells that were destroyed by chemotherapy. Plerixafor has orphan drug status in the United States and European Union; it was approved by the U.S. Food and Drug Administration on December 15, 2008.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 502.782
Monoisotopic: 502.447143768
Chemical Formula
C28H54N8
Synonyms
  • Plerixafor
External IDs
  • AMD-3100
  • AMD3100

Pharmacology

Indication

Used in combination with granulocyte-colony stimulating factor (G-CSF, filgrastim) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM).

Pharmacology
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Drug Discovery
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Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Plerixafor is a bicyclam derivative that antagonizes CXCR4 by binding to three acidic residues in the ligand-binding pocket: Asp171, Asp262, and Glu288. Blood levels of CD34+ cells peaked at 9 hours after administration of 0.24 mg/kg plerixafor in healthy subjects. In patients that have non-Hodgkin’s lymphoma or multiple myeloma, blood levels of CD34+ peaked at 6 hours. In combination with a G-CSF, circulating CD34+ cells in the peripheral blood peaked at 9-14 hours.

Mechanism of action

Plerixafor inhibits the CXCR4 chemokine receptors on CD34+ cells and reversibly blocks binding of the ligand, stromal cell-derived factor-1-alpha (SDF-1α). By blocking the interaction between SDF-1α and CXCR4 with plerixafor, mobilization of progenitor cells is triggered. Filgrastim, a granulocyte-colony stimulating factor, is added to enhance CD34+ cell mobilization, thus increasing the yield of stem cells- an important determinant of graft adequacy.

TargetActionsOrganism
AC-X-C chemokine receptor type 4
antagonist
Humans
Absorption

Pharmacokinetic profile follows a two-compartment model with first-order absorption. A median peak plasma concentration of 0.24 mg/kg of plerixafor occurred 30-60 minutes after subcutaneous dose.

Volume of distribution

0.3 L/kg

Protein binding

58%

Metabolism

Metabolism does not involved CYP isoenzymes

Route of elimination

0.24 mg/kg, healthy subjects: ~70% of the parent drug is excreted in urine in the first 24 hours.

Half-life

Terminal elimination half-life, NHL patients: 4.4 hours; Terminal elimination half-life, MM patients: 5.6 hours; Terminal elimination half-life, Hodgkin's lymphoma patients: 3.5 hours; Distribution half-life: 0.3 hours

Clearance

Total plasma clearance: 4.38 L/h; Renal clearance: 3.15 L/h

Adverse Effects
Medicalerrors
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Toxicity

LD50, mouse, SC: 16.3 mg/kg; LD50, rat, SC: >50 mg/kg; LD50, mouse and rat, IV injection: 5.2 mg/kg

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Plerixafor which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Plerixafor which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Plerixafor which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Plerixafor which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Plerixafor which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Plerixafor which could result in a higher serum level.
AclidiniumPlerixafor may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastinePlerixafor may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Plerixafor which could result in a higher serum level.
Adefovir dipivoxilAdefovir dipivoxil may decrease the excretion rate of Plerixafor which could result in a higher serum level.
Interactions
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Food Interactions
No interactions found.

Products

Products
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Product Ingredients
IngredientUNIICASInChI Key
Plerixafor octahydrochlorideOD49913540155148-31-5UEUPDYPUTTUXLJ-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MozobilInjection, solution20 mg/mlSubcutaneousGenzyme Europe Bv2020-12-23Not applicableEU flag
MozobilSolution24 mg/1.2mLSubcutaneoussanofi-aventis U.S. LLC2013-09-01Not applicableUS flag
MozobilSolution20 mg / mLSubcutaneousSanofi Aventis2012-03-26Not applicableCanada flag
MozobilSolution24 mg/1.2mLSubcutaneousGenzyme Corporation2008-12-152018-03-23US flag

Categories

ATC Codes
L03AX16 — Plerixafor
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylmethylamines. These are compounds containing a phenylmethtylamine moiety, which consists of a phenyl group substituted by an methanamine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylmethylamines
Direct Parent
Phenylmethylamines
Alternative Parents
Benzylamines / Aralkylamines / Trialkylamines / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Amine / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Benzylamine / Hydrocarbon derivative / Organic nitrogen compound / Organoheterocyclic compound / Organonitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
S915P5499N
CAS number
110078-46-1
InChI Key
YIQPUIGJQJDJOS-UHFFFAOYSA-N
InChI
InChI=1S/C28H54N8/c1-9-29-15-17-31-13-3-21-35(23-19-33-11-1)25-27-5-7-28(8-6-27)26-36-22-4-14-32-18-16-30-10-2-12-34-20-24-36/h5-8,29-34H,1-4,9-26H2
IUPAC Name
1-{[4-(1,4,8,11-tetraazacyclotetradecan-1-ylmethyl)phenyl]methyl}-1,4,8,11-tetraazacyclotetradecane
SMILES
C(N1CCCNCCNCCCNCC1)C1=CC=C(CN2CCCNCCNCCCNCC2)C=C1

References

General References
  1. Uy GL, Rettig MP, Cashen AF: Plerixafor, a CXCR4 antagonist for the mobilization of hematopoietic stem cells. Expert Opin Biol Ther. 2008 Nov;8(11):1797-804. doi: 10.1517/14712598.8.11.1797 . [Article]
  2. Fricker SP: A novel CXCR4 antagonist for hematopoietic stem cell mobilization. Expert Opin Investig Drugs. 2008 Nov;17(11):1749-60. doi: 10.1517/13543784.17.11.1749 . [Article]
  3. DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL, Maziarz RT, Hosing C, Fruehauf S, Horwitz M, Cooper D, Bridger G, Calandra G: Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009 Jun 4;113(23):5720-6. doi: 10.1182/blood-2008-08-174946. Epub 2009 Apr 10. [Article]
  4. Stewart DA, Smith C, MacFarland R, Calandra G: Pharmacokinetics and pharmacodynamics of plerixafor in patients with non-Hodgkin lymphoma and multiple myeloma. Biol Blood Marrow Transplant. 2009 Jan;15(1):39-46. doi: 10.1016/j.bbmt.2008.10.018. [Article]
  5. Brave M, Farrell A, Ching Lin S, Ocheltree T, Pope Miksinski S, Lee SL, Saber H, Fourie J, Tornoe C, Booth B, Yuan W, He K, Justice R, Pazdur R: FDA review summary: Mozobil in combination with granulocyte colony-stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation. Oncology. 2010;78(3-4):282-8. doi: 10.1159/000315736. Epub 2010 Jun 8. [Article]
  6. Choi HY, Yong CS, Yoo BK: Plerixafor for stem cell mobilization in patients with non-Hodgkin's lymphoma and multiple myeloma. Ann Pharmacother. 2010 Jan;44(1):117-26. doi: 10.1345/aph.1M380. Epub 2009 Dec 15. [Article]
  7. Keating GM: Plerixafor: a review of its use in stem-cell mobilization in patients with lymphoma or multiple myeloma. Drugs. 2011 Aug 20;71(12):1623-47. doi: 10.2165/11206040-000000000-00000. [Article]
Human Metabolome Database
HMDB0015681
KEGG Drug
D08971
PubChem Compound
65015
PubChem Substance
99443297
ChemSpider
58531
BindingDB
50035696
RxNav
733003
ChEBI
125354
ChEMBL
CHEMBL18442
ZINC
ZINC000022443609
PharmGKB
PA165958410
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Plerixafor
FDA label
Download (270 KB)
MSDS
Download (86.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentDiabetes1
4CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
4Unknown StatusTreatmentAutologous Stem Cell Transplantation1
3CompletedTreatmentFront Line Mobilization / Hodgkin's Disease or Multiple Myeloma / Non-Hodgkin's Lymphoma (NHL) / Transplantations1
3CompletedTreatmentMultiple Myeloma (MM)2
3CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)2
3TerminatedTreatmentRefractory Multiple Myeloma1
2Active Not RecruitingTreatmentScleroderma, Systemic1
2CompletedSupportive CareMultiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myeloid Leukemia (AML) / Hodgkins Disease (HD) / Leukemia Chronic Lymphocytic Leukemia (CLL) / Leukemia Chronic Myelogenous Leukemia (CML) / Myelodysplastic Syndromes (MDS) / Non-Hodgkin's Lymphoma (NHL) / Related Donors Donating PBSC to a Family Member1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionParenteral; Subcutaneous
Injection, solutionSubcutaneous20 mg/ml
SolutionSubcutaneous20 mg / mL
SolutionSubcutaneous24 mg/1.2mL
Injection, solution
SolutionSubcutaneous
SolutionSubcutaneous20 mg/ml
SolutionSubcutaneous24 mg
Injection, solutionSubcutaneous
Injection, solution20 mg/1ml
SolutionSubcutaneous20 mg/1ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6987102No2006-01-172023-07-22US flag
US7897590No2011-03-012023-03-22US flag
USRE42152No2011-02-152018-12-10US flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)131.5 °CFDA label
water solubilitySolubleMSDS
pKa6.0 - 7.5MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0472 mg/mLALOGPS
logP0.62ALOGPS
logP-0.43ChemAxon
logS-4ALOGPS
pKa (Strongest Basic)10.54ChemAxon
Physiological Charge4ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area78.66 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity155.01 m3·mol-1ChemAxon
Polarizability60.51 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.932
Blood Brain Barrier+0.6867
Caco-2 permeable-0.5403
P-glycoprotein substrateSubstrate0.8076
P-glycoprotein inhibitor INon-inhibitor0.8119
P-glycoprotein inhibitor IINon-inhibitor0.7683
Renal organic cation transporterInhibitor0.5069
CYP450 2C9 substrateNon-substrate0.8905
CYP450 2D6 substrateSubstrate0.5274
CYP450 3A4 substrateNon-substrate0.7818
CYP450 1A2 substrateNon-inhibitor0.8787
CYP450 2C9 inhibitorNon-inhibitor0.9272
CYP450 2D6 inhibitorNon-inhibitor0.7149
CYP450 2C19 inhibitorNon-inhibitor0.9114
CYP450 3A4 inhibitorNon-inhibitor0.8817
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.926
Ames testNon AMES toxic0.7906
CarcinogenicityNon-carcinogens0.9106
BiodegradationNot ready biodegradable0.9824
Rat acute toxicity2.1178 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5
hERG inhibition (predictor II)Inhibitor0.6334
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiq...
Gene Name
CXCR4
Uniprot ID
P61073
Uniprot Name
C-X-C chemokine receptor type 4
Molecular Weight
39745.055 Da
References
  1. Uy GL, Rettig MP, Cashen AF: Plerixafor, a CXCR4 antagonist for the mobilization of hematopoietic stem cells. Expert Opin Biol Ther. 2008 Nov;8(11):1797-804. doi: 10.1517/14712598.8.11.1797 . [Article]
  2. Jujo K, Ii M, Sekiguchi H, Klyachko E, Misener S, Tanaka T, Tongers J, Roncalli J, Renault MA, Thorne T, Ito A, Clarke T, Kamide C, Tsurumi Y, Hagiwara N, Qin G, Asahi M, Losordo DW: CXC-chemokine receptor 4 antagonist AMD3100 promotes cardiac functional recovery after ischemia/reperfusion injury via endothelial nitric oxide synthase-dependent mechanism. Circulation. 2013 Jan 1;127(1):63-73. doi: 10.1161/CIRCULATIONAHA.112.099242. Epub 2012 Nov 30. [Article]

Drug created on September 14, 2010 16:21 / Updated on August 04, 2021 18:23