etoposide phosphate 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
3944 117091-64-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • etoposide phosphate
  • etopofos
  • etopophos
Etoposide phosphate is a prodrug that is converted to its active moiety, etoposide, by dephosphorylation. Etoposide causes the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals, leading to cell cycle arrest, primarily at the G2 stage of the cell cycle, and cell death.
  • Molecular weight: 668.54
  • Formula: C29H33O16P
  • CLOGP: -0.87
  • LIPINSKI: 2
  • HAC: 16
  • HDO: 4
  • TPSA: 207.36
  • ALOGS: -2.97
  • ROTB: 7
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
S (Water solubility) 0.11 mg/mL Bocci G, Oprea TI, Benet LZ
BA (Bioavailability) 52 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -2.075 High 0.83
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.897 High 0.83
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.221 10^-6 cm/s High 0.83
dh-clint Dog hepatocyte intrinsic clearance 2.529 uL/min/10^6 cells High 0.83
dppb Dog plasma protein binding (% unbound) 46.320 % High 0.83
fcs-ppb Fetal calf serum protein binding (% unbound) 55.220 % High 0.83
herg hERG pIC50 4.527 pIC50 High 0.83
hh-clint Human hepatocyte intrinsic clearance 1.312 uL/min/10^6 cells High 0.83
hlm-clint Human liver microsomal intrinsic clearance 3.327 uL/min/mg protein High 0.83
hppb Human plasma protein binding (% unbound) 32.670 % High 0.83
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,GRK2,GSK3B,ITK,JAK2,JAK3,KDR,MAP2K6,MAP3K14,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,MTOR,NTRK2,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CG,PIM2,PRKDC,SIK2,STK33,SYK,TEK,TGFBR1,TTK,ZAP70 49
kinase-selectivity-class AXL,GRK2,MAP2K6 3
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 0.355 High 0.83
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.476 High 0.83
mh-clint Mouse hepatocyte intrinsic clearance 5.152 High 0.83
mppb Mouse plasma protein binding (% unbound) 40.890 High 0.83
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.019 High 0.83
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 0 High 0.83
pppb Pig plasma protein binding (% unbound) 42.970 % High 0.83
rat-kpuu-brain Rat brain Kpuu 0.001 % High 0.83
rh-clint Rat hepatocyte intrinsic clearance 2.799 uL/min/10^6 cells High 0.83
rh-fuinc Rat hepatocyte fraction unbound in incubation 81.430 % High 0.83
rppb Rat plasma protein binding (% unbound) 23.730 % High 0.83
solubility-dd Solubility at pH 7.4 in DMSO 935.406 uM High 0.83

Approvals:

DateAgencyCompanyOrphan
May 17, 1996 FDA BRISTOL MYERS SQUIBB

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
Disease progression 133.46 44.57 58 1255 156557 90470577
Dilatation intrahepatic duct acquired 93.19 44.57 15 1298 753 90626381
Venoocclusive liver disease 83.60 44.57 19 1294 5974 90621160
Pancytopenia 51.76 44.57 28 1285 120235 90506899

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
Disease progression 124.42 39.90 72 1459 143584 42476220
Second primary malignancy 65.83 39.90 21 1510 9554 42610250
Febrile bone marrow aplasia 64.57 39.90 21 1510 10160 42609644
Venoocclusive liver disease 52.39 39.90 18 1513 10284 42609520
Myelodysplastic syndrome 48.13 39.90 21 1510 22724 42597080
Bone marrow failure 43.53 39.90 22 1509 33071 42586733
Diffuse large B-cell lymphoma recurrent 43.19 39.90 13 1518 4873 42614931
Off label use 42.71 39.90 79 1452 638256 41981548

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
Venoocclusive liver disease 124.74 36.87 35 2663 15172 110571429
Disease progression 99.40 36.87 66 2632 243968 110342633
Febrile bone marrow aplasia 98.22 36.87 30 2668 17435 110569166
Dilatation intrahepatic duct acquired 83.94 36.87 15 2683 828 110585773
Bone marrow failure 72.61 36.87 33 2665 57815 110528786
Febrile neutropenia 65.08 36.87 57 2641 316710 110269891
Thrombocytopenia 56.54 36.87 55 2643 348830 110237771
Septic shock 50.84 36.87 37 2661 157491 110429110
Encephalopathy 43.07 36.87 26 2672 81029 110505572
Off label use 41.01 36.87 103 2595 1500082 109086519
Cardiotoxicity 39.38 36.87 15 2683 16866 110569735

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
FDA MoA N0000000176 Topoisomerase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D000972 Antineoplastic Agents, Phytogenic
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D059005 Topoisomerase II Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:59517 DNA synthesis inhibitor
FDA EPC N0000175609 Topoisomerase Inhibitor

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

DiseaseRelationSNOMED_IDDOID
Small cell carcinoma of lung indication 254632001 DOID:5409
Malignant tumor of testis indication 363449006 DOID:2998
Allogeneic bone marrow transplantation off-label use 58390007
Ewing's sarcoma off-label use 76909002 DOID:3369
Acute myeloid leukemia, disease off-label use 91861009
Kaposi's sarcoma off-label use 109385007
Diffuse non-Hodgkin's lymphoma, large cell off-label use 109969005
Multiple myeloma off-label use 109989006 DOID:9538
Hodgkin's disease off-label use 118599009
Burkitt's lymphoma off-label use 118617000
Non-small cell lung cancer off-label use 254637007 DOID:3908
Osteosarcoma of bone off-label use 307576001 DOID:3376
Neuroblastoma off-label use 432328008 DOID:769
Testicular Germ Cell Tumor off-label use
Ovarian Germ Cell Tumor Carcinoma off-label use
Neuroendocrine Prostate Carcinoma off-label use
Progressive Diffuse Large B-Cell Lymphoma off-label use
Acute hemorrhage contraindication 8573003
Fibrosis of lung contraindication 51615001 DOID:3770
Metabolic acidosis contraindication 59455009
Acute infectious disease contraindication 63171007
Interstitial pneumonia contraindication 64667001
Leukopenia contraindication 84828003 DOID:615
Hypoalbuminemia contraindication 119247004
Impaired renal function disorder contraindication 197663003
Drug-induced hepatitis contraindication 235876009
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 1.64 acidic
pKa2 6.69 acidic
pKa3 13.08 acidic
pKa4 13.86 acidic

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
DNA topoisomerase 2-alpha Enzyme INHIBITOR CHEMBL CHEMBL

External reference:

IDSource
4020979 VUID
N0000179127 NUI
D04107 KEGG_DRUG
4018141 VANDF
4020979 VANDF
C0059874 UMLSCUI
EVP PDB_CHEM_ID
CHEMBL1200645 ChEMBL_ID
C061400 MESH_SUPPLEMENTAL_RECORD_UI
528XYJ8L1N UNII
6918092 PUBCHEM_CID
24614 RXNORM
160598 MMSL
4209 MMSL
4709 MMSL
4710 MMSL
d00230 MMSL
d07388 MMSL
002674 NDDF
006055 NDDF
387316009 SNOMEDCT_US
426891005 SNOMEDCT_US
56928005 SNOMEDCT_US
C0015133 UMLSCUI
CHEBI:135867 CHEBI
DB00773 DRUGBANK_ID
36462 PUBCHEM_CID
3835 INN_ID
D005047 MESH_DESCRIPTOR_UI
CHEBI:4911 CHEBI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ETOPOPHOS HUMAN PRESCRIPTION DRUG LABEL 1 61269-410 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS NDA 18 sections