plerixafor ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
chemokine CXCR4 antagonists 4410 110078-46-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • plerixafor hydrochloride
  • plerixafor HCl
  • AMD3100
  • AMD 3100
  • plerixafor
  • mozobil
Plerixafor is an inhibitor of the CXCR4 chemokine receptor and blocks binding of its cognate ligand, stromal cell-derived factor-1alpha (SDF-1alpha). SDF-1alpha and CXCR4 are recognized to play a role in the trafficking and homing of human hematopoietic stem cells (HSCs) to the marrow compartment. Once in the marrow, stem cell CXCR4 can act to help anchor these cells to the marrow matrix, either directly via SDF-1ฮฑ or through the induction of other adhesion molecules. Treatment with plerixafor resulted in leukocytosis and elevations in circulating hematopoietic progenitor cells in mice, dogs and humans. CD34+ cells mobilized by plerixafor were capable of engraftment with long-term repopulating capacity up to one year in canine transplantation models.
  • Molecular weight: 502.80
  • Formula: C28H54N8
  • CLOGP: -0.25
  • LIPINSKI: 2
  • HAC: 8
  • HDO: 6
  • TPSA: 78.66
  • ALOGS: -4.03
  • ROTB: 4
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
16.80 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 10 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 70 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.77 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2A,ACVR2B,AKT2,AKT3,ALK,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK4,CDK5,CDK9,CHEK1,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,IRAK1,IRAK4,ITK,JAK1,JAK3,MAP2K6,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAPK7,MAPKAPK2,MARK4,MET,NTRK1,NTRK2,PDK2,PDK4,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ULK1 51
kinase-selectivity-class AKT1,AKT3,ALK,AXL,BRAF,CAMK2A,CAMK2B,CAMK2D,CDK4,CDK7,CHEK1,CSF1R,CSK,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,FLT3,GAK,INSR,IRAK1,IRAK4,JAK1,KIT,MAP3K7,MAP4K1,MAP4K3,MAP4K5,MAPK7,MARK4,MELK,NTRK1,PAK2,PAK4,PDPK1,PRKACA,PRKCD,PRKG1,SIK2,SIK3,STK33,STK4,SYK,TYRO3,ULK1,ULK2 47
pfas-class PFAS structural alert (1 = True, 0 = False) 0

Approvals:

DateAgencyCompanyOrphan
Dec. 15, 2008 FDA GENZYME
July 30, 2009 EMA Sanofi B.V.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Venoocclusive liver disease 69.17 35.74 16 1178 5977 90621276
Acute respiratory distress syndrome 55.96 35.74 19 1175 28667 90598586
Thrombocytopenia 54.67 35.74 34 1160 208691 90418562
Febrile neutropenia 52.39 35.74 30 1164 158319 90468934

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Brain teratoma 59.29 30.30 7 1092 14 42620222
Febrile neutropenia 54.63 30.30 42 1057 185661 42434575
Mucosal inflammation 53.99 30.30 26 1073 49348 42570888
Engraftment syndrome 35.33 30.30 8 1091 1382 42618854
Venoocclusive liver disease 34.06 30.30 12 1087 10290 42609946

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Febrile neutropenia 139.67 32.45 80 1878 316687 110270654
Mucosal inflammation 138.58 32.45 55 1903 96086 110491255
Venoocclusive liver disease 97.87 32.45 27 1931 15180 110572161
Thrombocytopenia 81.04 32.45 59 1899 348826 110238515
Blood stem cell harvest failure 56.65 32.45 8 1950 132 110587209
Engraftment syndrome 52.57 32.45 11 1947 1921 110585420
Ascites 50.39 32.45 27 1931 92781 110494560
Escherichia infection 42.66 32.45 16 1942 23800 110563541
Cytopenia 42.46 32.45 17 1941 30099 110557242
Herpes simplex 37.26 32.45 13 1945 15751 110571590
Noctiphobia 33.33 32.45 4 1954 16 110587325

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L03AX16 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSTIMULANTS
IMMUNOSTIMULANTS
Other immunostimulants
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D019380 Anti-HIV Agents
MeSH PA D044966 Anti-Retroviral Agents
FDA PE N0000178324 Increased Hematopoietic Stem Cell Mobilization
FDA EPC N0000178326 Hematopoietic Stem Cell Mobilizer
CHEBI has role CHEBI:35526 hypoglycemic agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50847 immunological adjuvant
CHEBI has role CHEBI:64946 anti-HIV agent
CHEBI has role CHEBI:75835 anti-anaemic agent
CHEBI has role CHEBI:145438 C-X-C chemokine receptor type 4 antagonist
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

L03AX Other immunostimulants 15 drugs
cridanimodelapegademaseglatiramer acetatehistamineleniolisiblentinanmavorixaformifamurtidemotixafortidepegademasepidotimodroquinimex show all 15 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Solid malignant tumours indication 81920005
Multiple myeloma indication 109989006 DOID:9538
Malignant lymphoma indication 118600007 DOID:0060058
Peripheral Mobilization of Hematopoietic Stem Cells indication
Nontraumatic splenic rupture contraindication 43325004
Leukemia, disease contraindication 93143009 DOID:1240
Leukocytosis contraindication 111583006
Impaired renal function disorder contraindication 197663003
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Breastfeeding (mother) contraindication 413712001




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.45 Basic
pKa2 10.85 Basic
pKa3 8.05 Basic
pKa4 7.33 Basic
pKa5 7.16 Basic
pKa6 6.94 Basic
pKa7 3.22 Basic
pKa8 2.61 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
C-X-C chemokine receptor type 4 GPCR PARTIAL AGONIST Ki 6.05 CHEMBL CHEMBL
Muscarinic acetylcholine receptor M2 GPCR Ki 5.99 CHEMBL
Alpha-2C adrenergic receptor GPCR Ki 5.75 CHEMBL
Histamine H3 receptor GPCR Ki 8.56 CHEMBL
C-C chemokine receptor type 2 GPCR IC50 10.40 CHEMBL
Stromal cell-derived factor 1 Cytokine IC50 8.24 CHEMBL
C-C chemokine receptor type 4 GPCR ANTAGONIST IC50 6.19 IUPHAR
Muscarinic acetylcholine receptor M1 GPCR Ki 6.09 CHEMBL
Atypical chemokine receptor 3 GPCR AGONIST EC50 6.85 IUPHAR
C-X-C chemokine receptor type 4 GPCR IC50 6.97 CHEMBL

External reference:

IDSource
D08971 KEGG_DRUG
4028232 VUID
N0000177944 NUI
4028232 VANDF
C1955474 UMLSCUI
CHEBI:125354 CHEBI
VH6 PDB_CHEM_ID
CHEMBL18442 ChEMBL_ID
DB06809 DRUGBANK_ID
C088327 MESH_SUPPLEMENTAL_RECORD_UI
844 IUPHAR_LIGAND_ID
8513 INN_ID
S915P5499N UNII
65015 PUBCHEM_CID
733003 RXNORM
159539 MMSL
26078 MMSL
360503 MMSL
d07372 MMSL
012924 NDDF
442206008 SNOMEDCT_US
442264009 SNOMEDCT_US
S915P5499N INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Mozobil HUMAN PRESCRIPTION DRUG LABEL 1 0024-5862 INJECTION, SOLUTION 24 mg SUBCUTANEOUS NDA 28 sections
Plerixafor HUMAN PRESCRIPTION DRUG LABEL 1 25021-416 INJECTION, SOLUTION 20 mg SUBCUTANEOUS ANDA 27 sections
Plerixafor HUMAN PRESCRIPTION DRUG LABEL 1 31722-373 INJECTION, SOLUTION 24 mg SUBCUTANEOUS ANDA 25 sections
Plerixafor HUMAN PRESCRIPTION DRUG LABEL 1 43598-308 SOLUTION 24 mg SUBCUTANEOUS ANDA 24 sections
Plerixafor Human Prescription Drug Label 1 55150-356 SOLUTION 24 mg SUBCUTANEOUS ANDA 25 sections
Plerixafor HUMAN PRESCRIPTION DRUG LABEL 1 65219-284 INJECTION, SOLUTION 24 mg SUBCUTANEOUS NDA AUTHORIZED GENERIC 26 sections
Plerixafor Human Prescription Drug Label 1 68083-155 INJECTION, SOLUTION 24 mg SUBCUTANEOUS ANDA 25 sections
plerixafor HUMAN PRESCRIPTION DRUG LABEL 1 70121-1694 INJECTION, SOLUTION 24 mg SUBCUTANEOUS ANDA 25 sections
PLERIXAFOR HUMAN PRESCRIPTION DRUG LABEL 1 70710-1208 INJECTION 24 mg SUBCUTANEOUS ANDA 22 sections
PLERIXAFOR HUMAN PRESCRIPTION DRUG LABEL 1 70771-1776 INJECTION 24 mg SUBCUTANEOUS ANDA 1 sections
Plerixafor HUMAN PRESCRIPTION DRUG LABEL 1 71288-155 SOLUTION 24 mg SUBCUTANEOUS ANDA 26 sections
Plerixafor HUMAN PRESCRIPTION DRUG LABEL 1 72162-2642 INJECTION, SOLUTION 24 mg SUBCUTANEOUS ANDA 25 sections
Plerixafor Human Prescription Drug Label 1 72205-249 INJECTION, SOLUTION 24 mg SUBCUTANEOUS ANDA 25 sections