Identification

Name
Mitoxantrone
Accession Number
DB01204  (APRD00371)
Type
Small Molecule
Groups
Approved, Investigational
Description

An anthracenedione-derived antineoplastic agent. [PubChem]

Structure
Thumb
Synonyms
  • 1,4-DIHYDROXY-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)-9,10-anthracenedione
  • Mitoxantrona
  • Mitoxantrone
  • Mitoxantronum
Product Ingredients
IngredientUNIICASInChI Key
Mitoxantrone hydrochlorideU6USW86RD070476-82-3ZAHQPTJLOCWVPG-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mitoxantrone InjectionSolution2 mgIntravenousFresenius Kabi2007-12-03Not applicableCanada
Mitoxantrone InjectionSolution2 mgIntravenousTeva2006-03-28Not applicableCanada
Mitoxantrone Injection USPSolution2 mgIntravenousPfizer2001-12-03Not applicableCanada
NovantroneLiquid2 mgIntravenousWyeth Ltd.1996-12-022005-08-10Canada
NovantroneInjection, solution30 mg/15mLIntravenousSerono, Inc.2006-02-162006-08-21Us
NovantroneInjection, solution20 mg/10mLIntravenousEmd Serono1987-12-232011-06-08Us
NovantroneInjection, solution25 mg/12.5mLIntravenousSerono, Inc.2006-02-162006-08-21Us
Novantrone Inj 2mg/mlLiquid2 mgIntravenousLederle Cyanamid Canada Inc.1984-12-311997-08-14Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MitoxantroneInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals2006-04-112010-05-31Us
mitoXANTRONEInjection, solution, concentrate2 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2006-04-11Not applicableUs
MitoxantroneInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals2006-04-112010-05-31Us
mitoXANTRONEInjection, solution, concentrate2 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2006-04-11Not applicableUs
MitoxantroneInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals2006-04-112010-05-31Us
mitoXANTRONEInjection, solution, concentrate2 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2006-04-11Not applicableUs
MitoxantroneInjection, solution2 mg/1mLIntravenousFresenius Kabi2006-04-11Not applicableUs
MitoxantroneInjection, solution, concentrate2 mg/1mLIntravenousHospira, Inc.2006-04-11Not applicableUs
Mitoxantrone HydrochlorideInjection, solution2 mg/1mLIntravenousPfizer Laboratories Div Pfizer Inc.2012-12-122016-12-31Us
Categories
UNII
BZ114NVM5P
CAS number
65271-80-9
Weight
Average: 444.4809
Monoisotopic: 444.200884648
Chemical Formula
C22H28N4O6
InChI Key
KKZJGLLVHKMTCM-UHFFFAOYSA-N
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
IUPAC Name
1,4-dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)-9,10-dihydroanthracene-9,10-dione
SMILES
OCCNCCNC1=C2C(=O)C3=C(O)C=CC(O)=C3C(=O)C2=C(NCCNCCO)C=C1

Pharmacology

Indication

For the treatment of secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis

Associated Conditions
Associated Therapies
Pharmacodynamics

Mitoxantrone has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2.

Mechanism of action

Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity.

TargetActionsOrganism
ADNA
intercalation
Human
ADNA topoisomerase 2-alpha
inhibitor
Human
Absorption

Poorly absorbed following oral administration

Volume of distribution
  • 1000 L/m2
Protein binding

78%

Metabolism

Hepatic

Route of elimination
Not Available
Half life

75 hours

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]
Toxicity

Severe leukopenia with infection.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Mitoxantrone.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Mitoxantrone.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Mitoxantrone is combined with 2-Methoxyethanol.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Mitoxantrone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Mitoxantrone.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Mitoxantrone.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Mitoxantrone.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Mitoxantrone is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Mitoxantrone.
AbataceptThe risk or severity of adverse effects can be increased when Mitoxantrone is combined with Abatacept.
Food Interactions
Not Available

References

Synthesis Reference
US4197249
General References
  1. Fox EJ: Management of worsening multiple sclerosis with mitoxantrone: a review. Clin Ther. 2006 Apr;28(4):461-74. [PubMed:16750460]
External Links
Human Metabolome Database
HMDB0015335
KEGG Compound
C11195
PubChem Compound
4212
PubChem Substance
46504608
ChemSpider
4067
BindingDB
67690
ChEBI
50729
ChEMBL
CHEMBL58
Therapeutic Targets Database
DAP000057
PharmGKB
PA450526
HET
MIX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mitoxantrone
ATC Codes
L01DB07 — Mitoxantrone
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
2fum / 2kgp / 4g0v / 4i41 / 6gh9
FDA label
Download (1.3 MB)
MSDS
Download (53.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAML Arising After Exposure to Genotoxic Injury / AML Arising From Antecedent Hematologic Disorder (AHD) / AML Arising From Myelodysplastic Syndrome (MDS) / Newly Diagnosed Acute Myeloid Leukemia (AML) / Untreated AML1
1Active Not RecruitingTreatmentAcute Myelogenous Leukaemia (AML)1
1Active Not RecruitingTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Untreated Adult Acute Myeloid Leukemia1
1Active Not RecruitingTreatmentAdult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A / Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL / Adult Acute Promyelocytic Leukemia With PML-RARA / Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA / Alkylating Agent-Related Acute Myeloid Leukemia / Recurrent Adult Acute Myeloid Leukemia / Refractory Acute Myeloid Leukemia1
1Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1Active Not RecruitingTreatmentLeukemias1
1Active Not RecruitingTreatmentRecurrent Adult Acute Myeloid Leukemia / Refractory Acute Myeloid Leukemia1
1CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemias1
1CompletedTreatmentAcute Lymphoid Leukemia Relapse / Acute Lymphoid Leukemia Relapse After Bone Marrow Transplant1
1CompletedTreatmentAcute Myelogenous Leukaemia (AML)1
1CompletedTreatmentAcute Myeloid Leukemia With Multilineage Dysplasia Following / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML)1
1CompletedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Recurrent Adult Acute Myeloid Leukemia1
1CompletedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Neoplasms, Malignant / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia1
1CompletedTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Recurrent Adult Acute Myeloid Leukemia1
1CompletedTreatmentCML / Leukemia Acute Myeloid Leukemia (AML) / Leukemias / Myeloid Leukemias1
1CompletedTreatmentCancer of the Ovary1
1CompletedTreatmentChildhood B Acute Lymphoblastic Leukemia / Childhood T Acute Lymphoblastic Leukemia / Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Lymphoblastic Lymphoma1
1CompletedTreatmentLeukemias3
1CompletedTreatmentLeukemias / Myelodysplastic Syndromes2
1CompletedTreatmentMetastatic Castration Resistant Prostate Cancer1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentProstate Cancer1
1Not Yet RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1RecruitingTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Childhood Acute Erythroleukemia (M6) / Childhood Acute Megakaryocytic Leukemia (M7) / Childhood Acute Monoblastic Leukemia (M5a) / Childhood Acute Monocytic Leukemia (M5b) / Childhood Acute Myeloblastic Leukemia With Maturation (M2) / Childhood Acute Myeloblastic Leukemia Without Maturation (M1) / Childhood Acute Myeloid Leukemia in Remission / Childhood Acute Myelomonocytic Leukemia (M4) / Recurrent Adult Acute Myeloid Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Untreated Adult Acute Myeloid Leukemia / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
1RecruitingTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML)1
1RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)2
1TerminatedTreatmentAcute Myelogenous Leukaemia (AML)1
1TerminatedTreatmentAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome / Adult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult Acute Megakaryoblastic Leukemia / Adult Acute Monoblastic Leukemia / Adult Acute Monocytic Leukemia / Adult Acute Myeloid Leukemia in Remission / Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With Maturation / Adult Acute Myeloid Leukemia With Minimal Differentiation / Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL / Adult Acute Myeloid Leukemia Without Maturation / Adult Acute Myelomonocytic Leukemia / Adult Erythroleukemia / Adult Pure Erythroid Leukemia / Alkylating Agent-Related Acute Myeloid Leukemia / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Untreated Adult Acute Myeloid Leukemia1
1TerminatedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Recurrent Adult Acute Myeloid Leukemia1
1TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)2
1Unknown StatusTreatmentProstate Cancer1
1, 2Active Not RecruitingTreatmentAcute Biphenotypic Leukemia (ABL) / De Novo Myelodysplastic Syndrome / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Secondary Myelodysplastic Syndromes / Untreated Adult Acute Myeloid Leukemia1
1, 2Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)3
1, 2Active Not RecruitingTreatmentLymphoma, Hodgkins1
1, 2CompletedTreatmentAdenocarcinoma of the Prostate / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
1, 2CompletedTreatmentCancer of the Ovary1
1, 2CompletedTreatmentCastrate-resistant Prostate Cancer (CRPC) / Malignancies / Mestastatic Prostate Cancer / Prostate Cancer1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2CompletedTreatmentLeukemias2
1, 2CompletedTreatmentLeukemias / Malignant Lymphomas1
1, 2CompletedTreatmentPreviously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia1
1, 2CompletedTreatmentRecurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Adult Acute Myeloid Leukemia1
1, 2CompletedTreatmentRelapsed/Refractory Acute Myeloid Leukemia (AML)1
1, 2RecruitingTreatmentAcute Biphenotypic Leukemia (ABL) / De Novo Myelodysplastic Syndrome / High Risk Myelodysplastic Syndrome / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Myeloproliferative Neoplasms1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Burkitt Lymphoma/Leukemia / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Lymphoma, Lymphoblastic1
1, 2RecruitingTreatmentHigh-Grade Myeloid Neoplasm / Leukemia Acute Myeloid Leukemia (AML)1
1, 2RecruitingTreatmentDe Novo Myelodysplastic Syndrome / Mixed Phenotype Acute Leukemia (MPAL) / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia / Recurrent High Risk Myelodysplastic Syndrome / Refractory Acute Myeloid Leukemia / Refractory High Risk Myelodysplastic Syndrome / Untreated Adult Acute Myeloid Leukemia1
1, 2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Precursor B-Cell Lymphoblastic Leukemia / Precursor T-Cell Lymphoblastic Leukemia1
1, 2TerminatedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Recurrent Adult Acute Myeloid Leukemia1
1, 2TerminatedTreatmentLeukemias1
1, 2Unknown StatusTreatmentMalignant Lymphomas1
1, 2Unknown StatusTreatmentProstate Cancer1
2Active Not RecruitingTreatmentMalignant Lymphomas1
2CompletedNot AvailableMesothelioma1
2CompletedDiagnosticRelapsing Remitting Multiple Sclerosis (RRMS)1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
2CompletedTreatmentAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentAdenocarcinoma of the Prostate / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
2CompletedTreatmentAdult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Recurrent Adult Acute Myeloid Leukemia1
2CompletedTreatmentAndrogen-independent Prostate Cancer1
2CompletedTreatmentCancer of the Ovary1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentCancer, Breast / Drug/Agent Toxicity by Tissue/Organ1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias1
2CompletedTreatmentFollicular Lymphoma (FL)2
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)2
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2CompletedTreatmentLeukemia, Prolymphocytic / Leukemias1
2CompletedTreatmentLeukemias10
2CompletedTreatmentLeukemias / Malignant Lymphomas1
2CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
2CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL) / Poor prognosis1
2CompletedTreatmentMalignant Lymphomas4
2CompletedTreatmentMantle Cell Lymphoma (MCL)1
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)2
2CompletedTreatmentProstate Cancer7
2CompletedTreatmentRelapsed or Refractory Mantle Cell Lymphoma (MCL)1
2CompletedTreatmentT-cell-prolymphocytic Leukemia1
2Enrolling by InvitationTreatmentAcute,Leukemia, Lymphoid1
2Not Yet RecruitingTreatmentFLT3-Mutated Acute Myeloid Leukemia1
2RecruitingBasic ScienceRecurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Untreated Adult Acute Myeloid Leukemia1
2RecruitingTreatmentAcute Leukemias of Ambiguous Lineage / Leukemia Acute Myeloid Leukemia (AML) / Myeloid Neoplasm1
2RecruitingTreatmentGranulocytic Sarcoma / Recurrent Adult Acute Myeloid Leukemia1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)2
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
2RecruitingTreatmentPediatric Acute Myeloid Leukemia1
2RecruitingTreatmentRecurrent B-Cell Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood B-Lymphoblastic Lymphoma1
2SuspendedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Leukemia, Lymphocytic1
2TerminatedNot AvailableRelapsing Remitting Multiple Sclerosis (RRMS)1
2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia, B-Cell / Leukemia, T-Cell / Non-Hodgkin's Lymphoma (NHL)1
2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
2TerminatedTreatmentAcute Lymphocytic Leukemia (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Mixed Lineage Acute Leukemia1
2TerminatedTreatmentFollicular Lymphoma (FL)2
2TerminatedTreatmentHigh-risk Myelodysplastic Syndrome (MDS) / Leukemia Acute Myeloid Leukemia (AML)1
2TerminatedTreatmentLeukemias1
2TerminatedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2TerminatedTreatmentMantle Cell Lymphoma (MCL)2
2TerminatedTreatmentMetastatic Hormone Refractory Prostate Cancer1
2TerminatedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
2TerminatedTreatmentProstate Cancer1
2TerminatedTreatmentProstatic Neoplasms2
2Unknown StatusSupportive CareDrug/Agent Toxicity by Tissue/Organ / Leukemias / Myelodysplastic Syndromes / Neutropenias1
2Unknown StatusTreatmentAcute Lymphoblastic Leukaemias (ALL) / Burkitts Leukemia/Lymphoma / Chronic Chronic myelogenous leukemia / Lymphoma, Lymphoblastic1
2Unknown StatusTreatmentCancer, Breast2
2Unknown StatusTreatmentDisseminated Sclerosis1
2Unknown StatusTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2Unknown StatusTreatmentLeukemias3
2Unknown StatusTreatmentMalignant Lymphomas1
2Unknown StatusTreatmentProstate Cancer1
2WithdrawnTreatmentMalignant Lymphomas1
2WithdrawnTreatmentProstate Cancer1
2, 3CompletedTreatmentProstate Cancer1
3Active Not RecruitingTreatmentChildhood Acute Promyelocytic Leukemia (M3) / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3Active Not RecruitingTreatmentDisseminated Sclerosis1
3Active Not RecruitingTreatmentGranulocytic Sarcoma / Leukaemia cutis / Leukemia Acute Myeloid Leukemia (AML) / Myeloid Neoplasm / Untreated Adult Acute Myeloid Leukemia / Untreated Childhood Myeloid Neoplasm1
3Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
3Active Not RecruitingTreatmentLeukemias1
3Active Not RecruitingTreatmentMalignant Lymphomas1
3Active Not RecruitingTreatmentProstate Cancer1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3CompletedTreatmentCancer, Breast3
3CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)2
3CompletedTreatmentLeukemia, Myelocytic, Acute1
3CompletedTreatmentLeukemias2
3CompletedTreatmentLeukemias / Malignant Lymphomas2
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes2
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms1
3CompletedTreatmentLeukemias / Neutropenias1
3CompletedTreatmentMalignant Lymphomas5
3CompletedTreatmentNeoplasms / Prostatic Neoplasms1
3CompletedTreatmentPain NOS / Prostate Cancer / Quality of Life1
3CompletedTreatmentProstate Cancer2
3CompletedTreatmentProstatic Neoplasms1
3Not Yet RecruitingTreatmentAcute Myeloid Leukemia, in Relapse1
3RecruitingTreatmentAcute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) Mutation1
3RecruitingTreatmentAcute Promyelocytic Leukemia (APL)1
3RecruitingTreatmentAcute Promyelocytic Leukemia With PML-RARA / Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA / Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA / Untreated Adult Acute Myeloid Leukemia / Untreated Childhood Myeloid Neoplasm1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentBlasts 5 Percent or More of Bone Marrow Nucleated Cells / Childhood Acute Myeloid Leukemia / Childhood Myelodysplastic Syndrome / Cytopenias / Down Syndrome (DS) / Myeloid Leukemia Associated With Down Syndrome / Myeloproliferative Neoplasms / Trisomy 21 Mosaicism1
3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)3
3RecruitingTreatmentRelapsed/Refractory Acute Myeloid Leukemia1
3RecruitingTreatmentRelapsed/Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations1
3TerminatedHealth Services ResearchFollicular Lymphoma (FL)1
3TerminatedTreatmentCancer of the Ovary1
3TerminatedTreatmentCastration Resistant Prostate Cancer (CRPC) / Pain NOS / Prostate Cancer / Prostatic Neoplasms1
3TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias1
3TerminatedTreatmentSecondary Progressive Multiple Sclerosis (SPMS)1
3Unknown StatusTreatmentIPI≥2 / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
3Unknown StatusTreatmentLeukemias3
3Unknown StatusTreatmentLeukemias / Malignant Lymphomas1
3Unknown StatusTreatmentLeukemias / Myelodysplastic Syndromes1
3Unknown StatusTreatmentLeukemias / Neutropenias1
3Unknown StatusTreatmentMalignant Lymphomas2
4Active Not RecruitingPreventionLeukemia Acute Myeloid Leukemia (AML)1
4Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4CompletedTreatmentAcute Promyelocytic Leukemia (APL)1
4CompletedTreatmentAdult Acute Lymphocytic Leukemia1
4CompletedTreatmentAutoimmune Diseases of the Nervous System / Demyelinating Autoimmune Diseases, CNS / Neuromyelitis Optica / Transverse Myelitis1
4RecruitingTreatmentChildhood Acute Promyelocytic Leukemia1
4Unknown StatusPreventionAcute Promyelocytic Leukemia (APL)1
4Unknown StatusTreatmentNeuromyelitis Optica / Neuromyelitis Optica Spectrum Disorders1
Not AvailableActive Not RecruitingTreatmentMalignant Lymphomas1
Not AvailableCompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
Not AvailableRecruitingTreatmentBlasts 10 Percent or More of Bone Marrow Nucleated Cells / Chronic Myelomonocytic Leukemia-2 / High Grade Malignant Neoplasm / Myelodysplastic Syndrome / Myelodysplastic Syndrome With Excess Blasts-2 / Myeloid Neoplasm / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Refractory Acute Myeloid Leukemia1
Not AvailableRecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
Not AvailableUnknown StatusTreatmentLeukemias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • APP Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • EMD Canada Inc.
  • Hospira Inc.
  • Otn Generics Inc.
  • Pierre Fabre
  • Sicor Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Wyeth Pharmaceuticals
Dosage forms
FormRouteStrength
Injection, solutionIntravenous2 mg/1mL
Injection, solution, concentrateIntravenous2 mg/1mL
SolutionIntravenous2 mg
Injection, solutionIntravenous20 mg/10mL
Injection, solutionIntravenous25 mg/12.5mL
Injection, solutionIntravenous30 mg/15mL
LiquidIntravenous2 mg
Prices
Unit descriptionCostUnit
Novantrone 2 mg/ml Concentrate 10ml Vial1649.32USD vial
Novantrone 2 mg/ml vial158.59USD ml
Mitoxantrone 20 mg/10 ml vial42.0USD ml
Mitoxantrone 25 mg/12.5 ml vial37.5USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
logP-3.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.734 mg/mLALOGPS
logP0.91ALOGPS
logP1.19ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)9.78ChemAxon
pKa (Strongest Basic)9.08ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count8ChemAxon
Polar Surface Area163.18 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity123.53 m3·mol-1ChemAxon
Polarizability48.49 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7557
Blood Brain Barrier-0.7979
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.8417
P-glycoprotein inhibitor INon-inhibitor0.8674
P-glycoprotein inhibitor IINon-inhibitor0.8381
Renal organic cation transporterNon-inhibitor0.7735
CYP450 2C9 substrateNon-substrate0.7907
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7013
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8544
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9211
Ames testAMES toxic0.9108
CarcinogenicityNon-carcinogens0.8742
BiodegradationNot ready biodegradable0.9727
Rat acute toxicity2.3061 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5839
hERG inhibition (predictor II)Inhibitor0.6894
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0012900000-147e3b4eed2bd9c29e51
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4j-0394000000-5f26812f41567533fe71

Taxonomy

Description
This compound belongs to the class of organic compounds known as anthraquinones. These are organic compounds containing either anthracene-9,10-quinone, 1,4-anthraquinone, or 1,2-anthraquinone.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Anthracenes
Sub Class
Anthraquinones
Direct Parent
Anthraquinones
Alternative Parents
Aryl ketones / Secondary alkylarylamines / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous amides / Vinylogous acids / 1,2-aminoalcohols / Dialkylamines / Primary alcohols / Organopnictogen compounds / Organic oxides
show 1 more
Substituents
9,10-anthraquinone / Anthraquinone / Aryl ketone / 1-hydroxy-2-unsubstituted benzenoid / Secondary aliphatic/aromatic amine / Vinylogous acid / Vinylogous amide / 1,2-aminoalcohol / Ketone / Secondary amine
show 13 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
hydroxyanthraquinones (CHEBI:50729)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Mazerski J, Martelli S, Borowski E: The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations. Acta Biochim Pol. 1998;45(1):1-11. [PubMed:9701490]
  2. Hajihassan Z, Rabbani-Chadegani A: Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins. J Biomed Sci. 2009 Mar 11;16:31. doi: 10.1186/1423-0127-16-31. [PubMed:19284573]
Details
2. DNA topoisomerase 2-alpha
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
Molecular Weight
174383.88 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Takeda K, Shinohara K, Kameda N, Ariyoshi K: A case of therapy-related acute myeloblastic leukemia with t(16;21)(q24;q22) after chemotherapy with DNA-topoisomerase II inhibitors, etoposide and mitoxantrone, and the alkylating agent, cyclophosphamide. Int J Hematol. 1998 Feb;67(2):179-86. [PubMed:9631585]
  3. McPherson JP, Deffie AM, Jones NR, Brown GA, Deuchars KL, Goldenberg GJ: Selective sensitization of adriamycin-resistant P388 murine leukemia cells to antineoplastic agents following transfection with human DNA topoisomerase II alpha. Anticancer Res. 1997 Nov-Dec;17(6D):4243-52. [PubMed:9494516]
  4. Wang H, Mao Y, Zhou N, Hu T, Hsieh TS, Liu LF: Atp-bound topoisomerase ii as a target for antitumor drugs. J Biol Chem. 2001 May 11;276(19):15990-5. Epub 2001 Feb 23. [PubMed:11278845]
  5. Satherley K, de Souza L, Neale MH, Alexander RA, Myatt N, Foss AJ, Hungerford JL, Hickson ID, Cree IA: Relationship between expression of topoisomerase II isoforms and chemosensitivity in choroidal melanoma. J Pathol. 2000 Oct;192(2):174-81. [PubMed:11004693]
  6. Mao Y, Yu C, Hsieh TS, Nitiss JL, Liu AA, Wang H, Liu LF: Mutations of human topoisomerase II alpha affecting multidrug resistance and sensitivity. Biochemistry. 1999 Aug 17;38(33):10793-800. [PubMed:10451375]
  7. Ko MW, Tamhankar MA, Volpe NJ, Porter D, McGrath C, Galetta SL: Acute promyelocytic leukemic involvement of the optic nerves following mitoxantrone treatment for multiple sclerosis. J Neurol Sci. 2008 Oct 15;273(1-2):144-7. doi: 10.1016/j.jns.2008.06.028. Epub 2008 Aug 6. [PubMed:18687447]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Zhou XJ, Zhou-Pan XR, Gauthier T, Placidi M, Maurel P, Rahmani R: Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions. Biochem Pharmacol. 1993 Feb 24;45(4):853-61. [PubMed:8452560]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Schrenk D, Michalke A, Gant TW, Brown PC, Silverman JA, Thorgeirsson SS: Multidrug resistance gene expression in rodents and rodent hepatocytes treated with mitoxantrone. Biochem Pharmacol. 1996 Nov 8;52(9):1453-60. [PubMed:8937457]
  2. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674]
  3. Taipalensuu J, Tavelin S, Lazorova L, Svensson AC, Artursson P: Exploring the quantitative relationship between the level of MDR1 transcript, protein and function using digoxin as a marker of MDR1-dependent drug efflux activity. Eur J Pharm Sci. 2004 Jan;21(1):69-75. [PubMed:14706813]
  4. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. doi: 10.1111/j.1349-7006.2009.01213.x. Epub 2009 May 12. [PubMed:19493273]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Morrow CS, Peklak-Scott C, Bishwokarma B, Kute TE, Smitherman PK, Townsend AJ: Multidrug resistance protein 1 (MRP1, ABCC1) mediates resistance to mitoxantrone via glutathione-dependent drug efflux. Mol Pharmacol. 2006 Apr;69(4):1499-505. Epub 2006 Jan 24. [PubMed:16434618]
  2. Diah SK, Smitherman PK, Aldridge J, Volk EL, Schneider E, Townsend AJ, Morrow CS: Resistance to mitoxantrone in multidrug-resistant MCF7 breast cancer cells: evaluation of mitoxantrone transport and the role of multidrug resistance protein family proteins. Cancer Res. 2001 Jul 15;61(14):5461-7. [PubMed:11454692]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Volk EL, Schneider E: Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43. [PubMed:14500392]
  2. Elahian F, Kalalinia F, Behravan J: Evaluation of indomethacin and dexamethasone effects on BCRP-mediated drug resistance in MCF-7 parental and resistant cell lines. Drug Chem Toxicol. 2010 Apr;33(2):113-9. doi: 10.3109/01480540903390000. [PubMed:20307139]
  3. Morrow CS, Peklak-Scott C, Bishwokarma B, Kute TE, Smitherman PK, Townsend AJ: Multidrug resistance protein 1 (MRP1, ABCC1) mediates resistance to mitoxantrone via glutathione-dependent drug efflux. Mol Pharmacol. 2006 Apr;69(4):1499-505. Epub 2006 Jan 24. [PubMed:16434618]
  4. Litman T, Brangi M, Hudson E, Fetsch P, Abati A, Ross DD, Miyake K, Resau JH, Bates SE: The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci. 2000 Jun;113 ( Pt 11):2011-21. [PubMed:10806112]
  5. Wang X, Furukawa T, Nitanda T, Okamoto M, Sugimoto Y, Akiyama S, Baba M: Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72. [PubMed:12488537]
  6. Sugimoto Y, Tsukahara S, Imai Y, Sugimoto Y, Ueda K, Tsuruo T: Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther. 2003 Jan;2(1):105-12. [PubMed:12533678]
  7. Maliepaard M, van Gastelen MA, de Jong LA, Pluim D, van Waardenburg RC, Ruevekamp-Helmers MC, Floot BG, Schellens JH: Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res. 1999 Sep 15;59(18):4559-63. [PubMed:10493507]
  8. Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A, Sarkadi B: Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun. 2001 Jul 6;285(1):111-7. [PubMed:11437380]
  9. Imai Y, Asada S, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y: Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol Pharmacol. 2003 Sep;64(3):610-8. [PubMed:12920197]
  10. Miwa M, Tsukahara S, Ishikawa E, Asada S, Imai Y, Sugimoto Y: Single amino acid substitutions in the transmembrane domains of breast cancer resistance protein (BCRP) alter cross resistance patterns in transfectants. Int J Cancer. 2003 Dec 10;107(5):757-63. [PubMed:14566825]
  11. Nakanishi T, Doyle LA, Hassel B, Wei Y, Bauer KS, Wu S, Pumplin DW, Fang HB, Ross DD: Functional characterization of human breast cancer resistance protein (BCRP, ABCG2) expressed in the oocytes of Xenopus laevis. Mol Pharmacol. 2003 Dec;64(6):1452-62. [PubMed:14645676]
  12. Allen JD, Van Dort SC, Buitelaar M, van Tellingen O, Schinkel AH: Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res. 2003 Mar 15;63(6):1339-44. [PubMed:12649196]
  13. Allen JD, Brinkhuis RF, Wijnholds J, Schinkel AH: The mouse Bcrp1/Mxr/Abcp gene: amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin. Cancer Res. 1999 Sep 1;59(17):4237-41. [PubMed:10485464]
  14. An Y, Ongkeko WM: ABCG2: the key to chemoresistance in cancer stem cells? Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1529-42. doi: 10.1517/17425250903228834. [PubMed:19708828]
  15. Paturi DK, Kwatra D, Ananthula HK, Pal D, Mitra AK: Identification and functional characterization of breast cancer resistance protein in human bronchial epithelial cells (Calu-3). Int J Pharm. 2010 Jan 15;384(1-2):32-8. doi: 10.1016/j.ijpharm.2009.09.037. Epub 2009 Sep 25. [PubMed:19782742]
  16. Ma Y, Wink M: The beta-carboline alkaloid harmine inhibits BCRP and can reverse resistance to the anticancer drugs mitoxantrone and camptothecin in breast cancer cells. Phytother Res. 2010 Jan;24(1):146-9. doi: 10.1002/ptr.2860. [PubMed:19548284]
  17. Mahringer A, Delzer J, Fricker G: A fluorescence-based in vitro assay for drug interactions with breast cancer resistance protein (BCRP, ABCG2). Eur J Pharm Biopharm. 2009 Aug;72(3):605-13. doi: 10.1016/j.ejpb.2009.01.010. [PubMed:19572416]
  18. Nicolle E, Boccard J, Guilet D, Dijoux-Franca MG, Zelefac F, Macalou S, Grosselin J, Schmidt J, Carrupt PA, Di Pietro A, Boumendjel A: Breast cancer resistance protein (BCRP/ABCG2): new inhibitors and QSAR studies by a 3D linear solvation energy approach. Eur J Pharm Sci. 2009 Aug 12;38(1):39-46. doi: 10.1016/j.ejps.2009.05.012. Epub 2009 Jun 6. [PubMed:19501160]
  19. Jani M, Szabo P, Kis E, Molnar E, Glavinas H, Krajcsi P: Kinetic characterization of sulfasalazine transport by human ATP-binding cassette G2. Biol Pharm Bull. 2009 Mar;32(3):497-9. [PubMed:19252303]
  20. Karla PK, Earla R, Boddu SH, Johnston TP, Pal D, Mitra A: Molecular expression and functional evidence of a drug efflux pump (BCRP) in human corneal epithelial cells. Curr Eye Res. 2009 Jan;34(1):1-9. doi: 10.1080/02713680802518251. [PubMed:19172464]
  21. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. doi: 10.1016/j.bcp.2009.04.002. Epub 2009 Apr 11. [PubMed:19427995]
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Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 06:47