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plerixafor ๐ถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| chemokine CXCR4 antagonists | 4410 | 110078-46-1 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
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.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 16.80 | mg | P |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| 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):
| Property | Description | Value | Unit | Confidence | Similarity |
|---|---|---|---|---|---|
| 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:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Dec. 15, 2008 | FDA | GENZYME | |
| July 30, 2009 | EMA | Sanofi B.V. |
FDA Adverse Event Reporting System (Female)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients 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 term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients 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 term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients 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:
| Source | Code | Description |
|---|---|---|
| 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
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| 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 |
๐ถ Veterinary Drug Use
None
๐ถ Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (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:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA 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:
| ID | Source |
|---|---|
| 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:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| 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 |