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Drug

D0084 | Mitoxantrone

Molecular Formula C22H28N4O6
Molecular Weight 444.5
Structure
State liquid
Clearance * 21.3 L/hr/m2 [Elderly patients with breast cancer receiving IV administration of 15-90 mg/m2] * 28.3 L/hr/m2 [Non-elderly patients with nasopharyngeal carcinoma receiving IV administration of 15-90 mg/m2] * 16.2 L/hr/m2 [Non-elderly patients with malignant lymphoma receiving IV administration of 15-90 mg/m2]
Volume of distribution * 1000 L/m2
Protein binding 0.78
Half life 75 hours
Absorption Poorly absorbed following oral administration

L

L01DB07 Mitoxantrone


[L01DB] Anthracyclines and related substances


[L01D] CYTOTOXIC ANTIBIOTICS AND RELATED SUBSTANCES


[L01] ANTINEOPLASTIC AGENTS


[L] Antineoplastic and immunomodulating agents

Toxicity Dose Time Species Model Method Action Positive criterion Reference
MEMBRANE POTENTIAL 7 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
RESPIRATION ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. Negative EC20 36
RESPIRATION ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
SWELLING ND 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) Negative EC20 36

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. Negative EC20 36
Succinate dehydrogenase ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
Cytochrome c > 400 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Warning

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.


H351 (100%): Suspected of causing cancer [Warning Carcinogenicity]


H411 (100%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]


 P201, P202, P273, P281, P308+P313, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Organism Test type Route Dose (normalized dose) Effect Source
mouse LD50 intraperitoneal 61300ug/kg (61.3mg/kg) National Cancer Institute Screening Program Data Summary, Developmental Therapeutics Program. Vol. JAN1986,
dog LDLo intravenous 25mg/kg (25mg/kg) National Technical Information Service. Vol. PB297-169,

  • Acute lymphocytic leukaemia

  • Acute myeloid leukaemia

  • Blast cell crisis

  • Chronic myeloid leukaemia

  • Disability

  • Hepatic cancer

  • Hepatic function abnormal

  • Hepatocellular carcinoma

  • Hormone-refractory prostate cancer

  • Leukaemia

  • Liver disorder

  • Lymphocytic leukaemia

  • Lymphoma

  • Metastatic neoplasm

  • Multiple sclerosis

  • Neoplasm malignant

  • Pain

  • Prostate cancer

  • Relapsing-remitting multiple sclerosis

  • Anxiety (0.05)

  • Vision blurred (0.03)

  • Abdominal pain

  • Abdominal pain upper

  • Agranulocytosis

  • Alanine aminotransferase increased

  • Alopecia

  • Amenorrhoea

  • Anaemia

  • Arrhythmia

  • Aspartate aminotransferase increased

  • Asthenia

  • Back pain

  • Blood glucose increased

  • Blood potassium decreased

  • Body temperature increased

  • Conjunctivitis

  • Constipation

  • Convulsion

  • Cough

  • Diarrhoea

  • Dyspnoea

  • Ecchymosis

  • Electrocardiogram abnormal

  • Foot and mouth disease

  • Fungal infection

  • Fungal skin infection

  • Gamma-glutamyltransferase increased

  • Gastrointestinal pain

  • Haemoglobin

  • Haemoglobin decreased

  • Haemorrhage

  • Headache

  • Infection

  • Jaundice

  • Leukopenia

  • Menorrhagia

  • Menstrual disorder

  • Mucosal inflammation

  • Musculoskeletal discomfort

  • Nausea

  • Petechiae

  • Pharyngitis

  • Platelet count decreased

  • Pneumonia

  • Renal failure

  • Rhinitis

  • Sepsis

  • Sinusitis

  • Stomatitis

  • Upper respiratory tract infection

  • Urinary tract infection

  • Urine abnormality

  • Urine analysis abnormal

  • Vomiting

  • White blood cell count decreased

    • 1,4-Bis(2-(2-hydroxyethylamino)ethyl)amino)-5,8-dihydroxyanthraquinone 1,4-Bis[[2-[(2-hydroxyethyl)amino]ethyl]imino]-1,4-dihydroanthracene-5,8,9,10-tetrol 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
    1,4-Dihydroxy-5,8-bis(2-((2-hydroxyethyl)amino)ethylamino)-9,10-anthracenedione 1,4-Dihydroxy-5,8-bis(5-hydroxy-3-azapentylamino)anthrachinon 1,4-Dihydroxy-5,8-bis-[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthraquinone
    1,4-Dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]anthracene-9,10-dione 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthracene-9,10-dione
    1,4-bis[2-(2-hydroxyethylamino)-ethylamino]-5,8-dihydroxyanthraquinone 1,4-bis[2-(2-hydroxyethylamino)ethylamino]-5,8-bis(oxidanyl)anthracene-9,10-dione;hydrochloride 1,4-bis[2-(2-hydroxyethylamino)ethylamino]-5,8-dihydroxyanthraquinone
    1,4-dihydroxy-5,8-bis(2-(2-hydroxyethylamino)ethylamino)anthracene-9,10-dione 1,4-dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)-9,10-dihydroanthracene-9,10-dione 1,4-dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthra-9,10-quinone
    1,4-dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthracene-9,10-dione 1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]-9,10-anthraquinone;hydrochloride 1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]-anthracene-9,10-dione
    1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]anthracene-9,10-dione;hydrochloride 1,4-dihydroxy-5,8-bis[2-[(1,1,2,2-tetradeuterio-2-hydroxyethyl)amino]ethylamino]anthracene-9,10-dione 1,4-dihydroxy-5,8-bis[[2-(2-hydroxyethylamino)ethyl]amino]anthraquinone
    13181-EP2270008A1 13181-EP2270505A1 13181-EP2272827A1
    13181-EP2275420A1 13181-EP2277876A1 13181-EP2289892A1
    13181-EP2292617A1 13181-EP2295055A2 13181-EP2295412A1
    13181-EP2295413A1 13181-EP2295416A2 13181-EP2295426A1
    13181-EP2295427A1 13181-EP2298748A2 13181-EP2298764A1
    13181-EP2298765A1 13181-EP2301928A1 13181-EP2305642A2
    13181-EP2305660A1 13181-EP2311453A1 13181-EP2311808A1
    13181-EP2311829A1 13181-EP2311837A1 13181-EP2311840A1
    13181-EP2311842A2 13181-EP2316832A1 13181-EP2316833A1
    13181-EP2316834A1 2fum 5,8-Bis((2-((2-hydroxyethyl)amino)ethyl)amino)-1,4-dihydroxyanthraquinone
    65271-80-9 71M809 9, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl] amino]-
    9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis((2-((2-hydroxyethyl)amino)ethyl)amino)- 9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis((2-((2-hydroxyethyl)amino)ethyl)amino)- (9CI) AB00053716
    AB00053716-18 AB00053716-19 AB00053716-22
    AB00053716_23 AB00053716_24 AK323601
    AKOS005564036 AN-584/42007670 ANTHRAQUINONE, 5,8-BIS((2-((2-HYDROXYETHYL)AMINO)ETHYL)AMINO)-1,4-DIHYDROXY-
    API0003408 AS-35321 BCP02861
    BCP9000931 BDBM67690 BIDD:PXR0181
    BPBio1_000627 BRD-K21680192-001-01-5 BRD-K21680192-001-11-4
    BRD-K21680192-300-05-2 BRD-K21680192-300-07-8 BRD-K21680192-300-09-4
    BRD-K21680192-300-10-2 BRD-K21680192-300-12-8 BRN 2795126
    BSPBio_000569 BSPBio_003160 BZ114NVM5P
    C11195 C22H28N4O6 CAS-70476-82-3
    CCG-36371 CCRIS 7604 CHEBI:50729
    CHEMBL58 CM0184 CS-2524
    CTK8A5416 D08224 DB01204
    DHAD DHAQ DHAQ (*Diacetate salt*)
    DTXSID4046947 Dihydroxyanthraquinone DivK1c_000516
    EBD32557 FT-0630752 GTPL7242
    HMS2090D05 HMS3655E20 HY-13502
    IDI1_000516 Immunex (Salt/Mix) K061
    KBio1_000516 KBio2_002135 KBio2_004703
    KBio2_007271 KBio3_002660 KBioGR_001531
    KBioSS_002135 KKZJGLLVHKMTCM-UHFFFAOYSA-N KSC-19-204
    KUC108634N LS-20638 Liposome Encapsulated Mitoxantrone (LEM)
    Lopac-M-6545 Lopac0_000779 MCULE-5513787065
    MFCD00242942 (95%) MITOXANTRONE, Mitoxantrone Hydrochloride, Mitoxantrone dihydrochloride, MITOXANTHRONE HYDROCHLORIDE MIX
    MLS001333711 MLS002703044 Misostol (TN)
    Mitoxanthrone Mitoxantron Mitoxantrona
    Mitoxantrona [INN-Spanish] Mitoxantrone (INN) Mitoxantrone (free base)
    Mitoxantrone [INN:BAN] Mitoxantrone [INN] Mitoxantrone hydrochloride (Salt/Mix)
    Mitoxantronum Mitoxantronum [INN-Latin] Mitozantrone
    Mitozantrone|||Novantron|||CL-232325|||1,4-Dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]anthracene-9,10-dione NCGC00015693-01 NCGC00015693-02
    NCGC00015693-03 NCGC00015693-04 NCGC00015693-05
    NCGC00015693-06 NCGC00015693-08 NCGC00162251-01
    NCI60_002276 NCI60_002535 NINDS_000516
    NSC 279836 NSC-279836 NSC-287836
    NSC-299195 NSC-301739D NSC279836
    NSC299195 NSC301739 Neuro_000153
    Novantrone Novantrone(R) (mitoxantrone for injection concentrate) Prestwick0_000385
    Prestwick1_000385 Prestwick2_000385 Prestwick3_000385
    Q239426 SBI-0050757.P003 SC-22733
    SCHEMBL3000 SMP2_000179 SMR000058480
    SMR001549953 SPBio_000756 SPBio_002490
    SR-01000076001 SR-01000076001-7 STK631833
    SW196745-6 SY226320 Spectrum2_000908
    Spectrum3_001590 Spectrum4_000866 Spectrum5_001205
    Spectrum_001655 TX-017756 UNII-BZ114NVM5P
    VU0244399-2 ZINC3794794 cid_4212
    cid_5458171 mitoxantrone s1889

    DrugBank Name Mitoxantrone
    DrugBank DB01204
    CAS Number 65271-80-9, 70476-82-3, 70711-41-0
    PubChem Compound 4212
    KEGG Compound ID C11195
    KEGG Drug D08224
    PubChem.Substance 46504608
    ChEBI 50729
    PharmGKB PA450526
    ChemSpider 4067
    BindingDB 67690.0
    TTD DAP000057
    Wikipedia Mitoxantrone
    HET MIX
    DPD 11343

    1. Dykens et al. (2007)