mitoxantrone Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antineoplastics; anthraquinone derivatives 1821 65271-80-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • mitoxantrone
  • mitoxantrone hydrochloride
  • dihydroxyanthraquinone
  • mitoxanthrone
  • mitozantrone
  • nimitoxantron
  • mitoxantrone dihydrochloride
  • mitoxantrone HCl
An anthracenedione-derived antineoplastic agent.
  • Molecular weight: 444.49
  • Formula: C22H28N4O6
  • CLOGP: 2.30
  • LIPINSKI: 1
  • HAC: 10
  • HDO: 8
  • TPSA: 163.18
  • ALOGS: -2.78
  • ROTB: 12

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 7.50 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 7 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.78 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 0 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 12 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 7.90 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.25 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 53 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 23, 1987 FDA

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
Febrile neutropenia 454.30 68.68 106 795 10776 2346408
Acute myeloid leukaemia 256.35 68.68 52 849 2658 2354526
Sepsis 246.06 68.68 73 828 18415 2338769
Myelodysplastic syndrome 229.50 68.68 47 854 2513 2354671
Neutropenia 161.21 68.68 55 846 21493 2335691
Second primary malignancy 141.76 68.68 27 874 979 2356205
Acute promyelocytic leukaemia 133.46 68.68 21 880 237 2356947
Pancytopenia 129.25 68.68 40 861 11412 2345772
Thrombocytopenia 116.61 68.68 42 859 19089 2338095
Pneumonia 110.88 68.68 53 848 49243 2307941
Haemophagocytic lymphohistiocytosis 103.97 68.68 22 879 1361 2355823
Pyrexia 100.62 68.68 51 850 53657 2303527
Bone marrow failure 99.78 68.68 28 873 5658 2351526
Febrile bone marrow aplasia 96.05 68.68 19 882 838 2356346
Leukaemia recurrent 90.59 68.68 15 886 237 2356947
Colitis 88.34 68.68 25 876 5201 2351983
Chronic hepatitis 80.23 68.68 13 888 178 2357006
Hypotension 76.09 68.68 36 865 32400 2324784
Respiratory failure 75.92 68.68 28 873 13500 2343684
Cardiac failure 75.18 68.68 27 874 12067 2345117
Lower respiratory tract infection fungal 70.65 68.68 10 891 50 2357134

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
Febrile neutropenia 619.02 62.73 154 878 10946 1734803
Myelodysplastic syndrome 281.16 62.73 65 967 3224 1742525
Acute myeloid leukaemia 264.64 62.73 61 971 2980 1742769
Neutropenia 235.19 62.73 82 950 18178 1727571
Septic shock 162.38 62.73 51 981 8058 1737691
Bone marrow failure 161.84 62.73 46 986 5154 1740595
Thrombocytopenia 130.89 62.73 56 976 21193 1724556
Pneumonia 127.19 62.73 70 962 46112 1699637
Sepsis 118.87 62.73 51 981 19387 1726362
Pyrexia 113.17 62.73 65 967 46335 1699414
Mucosal inflammation 94.91 62.73 29 1003 4140 1741609
Second primary malignancy 90.45 62.73 21 1011 1038 1744711
Respiratory failure 88.29 62.73 38 994 14467 1731282
Pancytopenia 86.76 62.73 35 997 11322 1734427
Colitis 78.05 62.73 25 1007 4155 1741594
Multiple organ dysfunction syndrome 72.31 62.73 29 1003 9213 1736536
Bacteraemia 69.10 62.73 19 1013 1861 1743888
Ameloblastoma 68.78 62.73 9 1023 7 1745742
Acute lymphocytic leukaemia recurrent 65.98 62.73 13 1019 289 1745460
Hypertensive hydrocephalus 63.19 62.73 8 1024 3 1745746

Pharmacologic Action:

SourceCodeDescription
ATC L01DB07 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
CYTOTOXIC ANTIBIOTICS AND RELATED SUBSTANCES
Anthracyclines and related substances
FDA EPC N0000175609 Topoisomerase Inhibitor
FDA MoA N0000000176 Topoisomerase Inhibitors
MeSH PA D000700 Analgesics
MeSH PA D000970 Antineoplastic Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018689 Sensory System Agents
CHEBI has role CHEBI:35480 analgesic
CHEBI has role CHEBI:35610 antineoplastic agent
MeSH PA D059005 Topoisomerase II Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Acute myeloid leukemia, disease indication 91861009
Relapsing remitting multiple sclerosis indication 426373005 DOID:2378
Metastatic Prostate Carcinoma indication
Follicular non-Hodgkin's lymphoma off-label use 308121000
Metastatic Breast Carcinoma off-label use
Progressive Diffuse Large B-Cell Lymphoma off-label use
Mycosis contraindication 3218000 DOID:1564
Viral disease contraindication 34014006 DOID:934
Chronic heart failure contraindication 48447003
Hepatic failure contraindication 59927004
Acute infectious disease contraindication 63171007
Leukopenia contraindication 84828003 DOID:615
Left heart failure contraindication 85232009
Bacterial infectious disease contraindication 87628006
Radiation oncology AND/OR radiotherapy contraindication 108290001
Acute disease of cardiovascular system contraindication 128487001
Seizure disorder contraindication 128613002
Disease of liver contraindication 235856003 DOID:409
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

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.37 acidic
pKa2 10.7 acidic
pKa3 9.13 Basic
pKa4 8.52 Basic
pKa5 4.01 Basic
pKa6 1.49 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
DNA topoisomerase 2-alpha Enzyme INHIBITOR IC90 5.96 WOMBAT-PK CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel Ki 5.53 DRUG MATRIX
Sodium-dependent noradrenaline transporter Transporter Ki 5.31 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 5.73 DRUG MATRIX
Muscarinic acetylcholine receptor M1 GPCR Ki 6.74 DRUG MATRIX
Muscarinic acetylcholine receptor M2 GPCR Ki 7.11 DRUG MATRIX
Muscarinic acetylcholine receptor M4 GPCR Ki 7.05 DRUG MATRIX
Epidermal growth factor receptor Kinase IC50 5.27 DRUG MATRIX
Tyrosine-protein kinase Fyn Kinase IC50 5.90 DRUG MATRIX
Receptor tyrosine-protein kinase erbB-2 Kinase IC50 5.69 DRUG MATRIX
ATP-binding cassette sub-family G member 2 Transporter Kact 5.15 WOMBAT-PK
Multidrug resistance-associated protein 1 Transporter IC50 6.29 WOMBAT-PK
Canalicular multispecific organic anion transporter 1 Transporter WOMBAT-PK
Multidrug resistance protein 1 Transporter IC50 5.84 WOMBAT-PK
Solute carrier family 22 member 3 Transporter IC50 4.22 CHEMBL
Solute carrier family 22 member 1 Transporter IC50 4.36 CHEMBL
Solute carrier family 22 member 2 Transporter IC50 4.13 CHEMBL
Tyrosine-protein kinase BTK Kinase IC50 6 CHEMBL
Serine/threonine-protein kinase pim-1 Kinase IC50 7.29 CHEMBL
Multidrug and toxin extrusion protein 2 Transporter IC50 6.28 CHEMBL
Multidrug and toxin extrusion protein 1 Transporter IC50 6.72 CHEMBL
DNA-3-methyladenine glycosylase Enzyme IC50 5.60 CHEMBL
Arachidonate 15-lipoxygenase Enzyme IC50 5.75 DRUG MATRIX
Integrase Enzyme IC50 5.42 CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 1A Unclassified AC50 5.02 CHEMBL

External reference:

IDSource
4019842 VUID
N0000147929 NUI
C0026259 UMLSCUI
D02166 KEGG_DRUG
108791001 SNOMEDCT_US
386913001 SNOMEDCT_US
4019842 VANDF
7005 RXNORM
d00306 MMSL
004828 NDDF
BZ114NVM5P UNII
4922 INN_ID
CHEMBL58 ChEMBL_ID
70476-82-3 SECONDARY_CAS_RN
MIX PDB_CHEM_ID
DB01204 DRUGBANK_ID
CHEBI:50729 CHEBI
CHEMBL1417019 ChEMBL_ID
D008942 MESH_DESCRIPTOR_UI
4212 PUBCHEM_CID
7242 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
mitoXANTRONE HUMAN PRESCRIPTION DRUG LABEL 1 0703-4680 INJECTION, SOLUTION, CONCENTRATE 2 mg INTRAVENOUS ANDA 15 sections
mitoXANTRONE HUMAN PRESCRIPTION DRUG LABEL 1 0703-4685 INJECTION, SOLUTION, CONCENTRATE 2 mg INTRAVENOUS ANDA 15 sections
mitoXANTRONE HUMAN PRESCRIPTION DRUG LABEL 1 0703-4686 INJECTION, SOLUTION, CONCENTRATE 2 mg INTRAVENOUS ANDA 15 sections
Mitoxantrone HUMAN PRESCRIPTION DRUG LABEL 1 61703-343 INJECTION, SOLUTION, CONCENTRATE 2 mg INTRAVENOUS ANDA 16 sections
Mitoxantrone HUMAN PRESCRIPTION DRUG LABEL 1 63323-132 INJECTION, SOLUTION 2 mg INTRAVENOUS ANDA 15 sections