Details of the Drug

General Information of Drug (ID: DMM39BF)

• Drug Name: Mitoxantrone
• Synonyms: DHAD; DHAQ; Dihydroxyanthraquinone; MIX; Misostol; Mitoxanthrone; Mitoxantron; Mitoxantrona; Mitoxantronum; Mitozantrone; DHAQ HCl; Mitoxantrone [INN]; Mitozantrone hydrochloride; Mitoxantrone 2HCl; Liposome Encapsulated Mitoxantrone (LEM); Misostol (TN); Mitoxantrona [INN-Spanish]; Mitoxantrone (INN); Mitoxantrone (free base); Mitoxantronum [INN-Latin]; Novantrone (TN); AN-584/42007670; Novantrone(R) (mitoxantrone for injection concentrate); DHAQ (*Diacetate salt*); MITOXANTRONE, Mitoxantrone Hydrochloride, Mitoxantrone dihydrochloride, MITOXANTHRONE HYDROCHLORIDE; MITOXANTRONE, 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)ANTHRA-9,10-QUINONE; 1,4-Bis(2-(2-hydroxyethylamino)ethyl)amino)-5,8-dihydroxyanthraquinone; 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-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)anthra-9,10-quinone; 1,4-dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthracene-9,10-dione; 5,8-Bis((2-((2-hydroxyethyl)amino)ethyl)amino)-1,4-dihydroxyanthraquinone; 9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis((2-((2-hydroxyethyl)amino)ethyl)amino)-(9CI)

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Approved	[1], [2]
Non-hodgkin lymphoma	2B33.5	Phase 1/2	[3]

• Therapeutic Class: Analgesics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 444.5
  Topological Polar Surface Area (xlogp); 1
  Rotatable Bond Count (rotbonds); 12
  Hydrogen Bond Donor Count (hbonddonor); 8
  Hydrogen Bond Acceptor Count (hbondacc); 10
• ADMET Property:
  Absorption: The drug is poorly absorbed following oral administration [4]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [5]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 7.9 mL/min/kg [6]
  Elimination: 7% of drug is excreted from urine in the unchanged form [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 75 hours [6]
  Metabolism: The drug is metabolized via the hepatic [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.7784 micromolar/kg/day [7]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.25% [6]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 12 L/kg [6]
  Water Solubility: The ability of drug to dissolve in water is measured as 7.5 mg/mL [5]
• Chemical Identifiers:
  Formula: C22H28N4O6
  IUPAC Name: 1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]anthracene-9,10-dione
  Canonical SMILES: C1=CC(=C2C(=C1NCCNCCO)C(=O)C3=C(C=CC(=C3C2=O)O)O)NCCNCCO
  InChI: InChI=1S/C22H28N4O6/c27-11-9-23-5-7-25-13-1-2-14(26-8-6-24-10-12-28)18-17(13)21(31)19-15(29)3-4-16(30)20(19)22(18)32/h1-4,23-30H,5-12H2
  InChIKey: KKZJGLLVHKMTCM-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4212
  ChEBI ID: CHEBI:50729
  CAS Number: 65271-80-9
  DrugBank ID: DB01204
  TTD ID: D0R3JB
  VARIDT ID: DR00269
  INTEDE ID: DR1102

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[8]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
ATP-binding cassette sub-family A member 3 (ABCA3)	DT2T6VQ	ABCA3_HUMAN	Substrate	[9]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[10]
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[11]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[12]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2E1 (CYP2E1) Main DME	DEVDYN7	CP2E1_HUMAN	Substrate	[13]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Mitoxantrone (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Moderate	Accelerated clearance of Mitoxantrone due to the transporter induction by Arn-509.	Acute myeloid leukaemia [2A60]	[64]
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Mitoxantrone and Roflumilast.	Asthma [CA23]	[64]
Sparfloxacin	DMB4HCT	Minor	Decreased absorption of Mitoxantrone due to intestinal mucosa variation caused by Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[65]
ABT-492	DMJFD2I	Minor	Decreased absorption of Mitoxantrone due to intestinal mucosa variation caused by ABT-492.	Bacterial infection [1A00-1C4Z]	[65]
Fostemsavir	DM50ILT	Moderate	Decreased clearance of Mitoxantrone due to the transporter inhibition by Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[66]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Mitoxantrone and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[67]
Denosumab	DMNI0KO	Moderate	Additive myelosuppressive effects by the combination of Mitoxantrone and Denosumab.	Low bone mass disorder [FB83]	[68]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of Mitoxantrone due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[69]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Mitoxantrone and Tecfidera.	Multiple sclerosis [8A40]	[70]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Mitoxantrone and Siponimod.	Multiple sclerosis [8A40]	[71]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Mitoxantrone and Fingolimod.	Multiple sclerosis [8A40]	[72]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Mitoxantrone and Ocrelizumab.	Multiple sclerosis [8A40]	[73]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Mitoxantrone and Ozanimod.	Multiple sclerosis [8A40]	[64]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive myelosuppressive effects by the combination of Mitoxantrone and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[74]
Enzalutamide	DMGL19D	Moderate	Accelerated clearance of Mitoxantrone due to the transporter induction by Enzalutamide.	Prostate cancer [2C82]	[75]
Darolutamide	DMV7YFT	Moderate	Decreased clearance of Mitoxantrone due to the transporter inhibition by Darolutamide.	Prostate cancer [2C82]	[76]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Mitoxantrone and Canakinumab.	Rheumatoid arthritis [FA20]	[77]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Mitoxantrone and Rilonacept.	Rheumatoid arthritis [FA20]	[77]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Mitoxantrone and Golimumab.	Rheumatoid arthritis [FA20]	[78]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Mitoxantrone when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[79]
Eltrombopag	DMOGFIX	Moderate	Decreased clearance of Mitoxantrone due to the transporter inhibition by Eltrombopag.	Thrombocytopenia [3B64]	[80]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Mitoxantrone and Valganciclovir.	Virus infection [1A24-1D9Z]	[71]

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