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Identification
- Summary
Mitoxantrone is a chemotherapeutic agent used for the treatment of secondary progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis.
- Generic Name
- Mitoxantrone
- DrugBank Accession Number
- DB01204
- Background
An anthracenedione-derived antineoplastic agent.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Mitoxantrone (DB01204)
- Weight
- Average: 444.4809
Monoisotopic: 444.200884648 - Chemical Formula
- C22H28N4O6
- Synonyms
- 1,4-Bis(2-(2-hydroxyethylamino)ethyl)amino)-5,8-dihydroxyanthraquinone
- Mitoxantrona
- Mitoxantrone
- Mitoxantronum
Pharmacology
- Indication
For the treatment of secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Acute lymphocytic leukemia ••• ••••• Treatment of Acute myelogenous leukemia ••• ••••• ••••••••• Used in combination to treat Acute myeloid leukemia •••••••••••• Treatment of Acute promyelocytic leukemia ••• ••••• ••••••••• Treatment of Hodgkin lymphoma ••• ••••• - Associated Therapies
- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism ADNA topoisomerase 2-beta modulatorHumans ADNA intercalationHumans ADNA topoisomerase 2-alpha inhibitorHumans - 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]
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Severe leukopenia with infection.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Mitoxantrone is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Mitoxantrone. Abemaciclib Abemaciclib may decrease the excretion rate of Mitoxantrone which could result in a higher serum level. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Mitoxantrone. Acetaminophen The metabolism of Acetaminophen can be increased when combined with Mitoxantrone. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Mitoxantrone hydrochloride U6USW86RD0 70476-82-3 ZAHQPTJLOCWVPG-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mitoxantrone Injection Solution 2 mg / mL Intravenous Teva Italia S.R.L. 2006-03-28 2018-07-09 Canada 
Mitoxantrone Injection Solution 2 mg / mL Intravenous Fresenius Kabi Italia S.R.L. 2007-12-03 Not applicable Canada Mitoxantrone Injection USP Solution 2 mg / mL Intravenous Pfizer Italia S.R.L. 2001-12-03 2019-03-26 Canada Novantrone Injection, solution 30 mg/15mL Intravenous Serono Europe Limited 2006-02-16 2006-08-21 US 
Novantrone Injection, solution 25 mg/12.5mL Intravenous Serono Europe Limited 2006-02-16 2006-08-21 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mitoxantrone Injection, solution 2 mg/1mL Intravenous Bedford Pharmaceuticals 2006-04-11 2010-05-31 US Mitoxantrone Injection, solution, concentrate 2 mg/1mL Intravenous Hospira, Inc. 2006-04-11 Not applicable US mitoXANTRONE Injection, solution, concentrate 2 mg/1mL Intravenous Teva Parenteral Medicines, Inc. 2006-04-11 Not applicable US Mitoxantrone Injection, solution 2 mg/1mL Intravenous Bedford Pharmaceuticals 2006-04-11 2010-05-31 US mitoXANTRONE Injection, solution, concentrate 2 mg/1mL Intravenous Teva Parenteral Medicines, Inc. 2006-04-11 Not applicable US
Categories
- ATC Codes
- L01DB07 — Mitoxantrone
- Drug Categories
- Analgesics
- Anthracenes
- Anthracyclines and Related Substances
- Anthraquinones
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Cardiotoxic antineoplastic agents
- Central Nervous System Agents
- Cytochrome P-450 CYP2E1 Inducers
- Cytochrome P-450 CYP2E1 Inducers (weak)
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Cytotoxic Antibiotics and Related Substances
- Enzyme Inhibitors
- Immunosuppressive Agents
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- P-glycoprotein inducers
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Peripheral Nervous System Agents
- Quinones
- Sensory System Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- 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
- 1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / 9,10-anthraquinone / Alcohol / Alkanolamine / Amine / Anthraquinone / Aromatic homopolycyclic compound / Aryl ketone / Hydrocarbon derivative show 13 more
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- hydroxyanthraquinones (CHEBI:50729)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- BZ114NVM5P
- CAS number
- 65271-80-9
- 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=CC=C(NCCNCCO)C2=C1C(=O)C1=C(C(O)=CC=C1O)C2=O
References
- Synthesis Reference
- US4197249
- General References
- Fox EJ: Management of worsening multiple sclerosis with mitoxantrone: a review. Clin Ther. 2006 Apr;28(4):461-74. [Article]
- External Links
- Human Metabolome Database
- HMDB0015335
- KEGG Drug
- D08224
- KEGG Compound
- C11195
- PubChem Compound
- 4212
- PubChem Substance
- 46504608
- ChemSpider
- 4067
- BindingDB
- 67690
- 7005
- ChEBI
- 50729
- ChEMBL
- CHEMBL58
- ZINC
- ZINC000003794794
- Therapeutic Targets Database
- DAP000057
- PharmGKB
- PA450526
- PDBe Ligand
- MIX
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Mitoxantrone
- PDB Entries
- 2fum / 2kgp / 4g0v / 4i41 / 6gh9 / 6vxi / 7nfd / 7r2g
- FDA label
- Download (1.3 MB)
- MSDS
- Download (53.2 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Mesothelioma 1 somestatus stop reason just information to hide Not Available Completed Treatment Acute Myeloid Leukemia 1 somestatus stop reason just information to hide Not Available Not Yet Recruiting Treatment Autologous Stem Cell Transplantation / Conditioning 1 somestatus stop reason just information to hide Not Available Not Yet Recruiting Treatment Breast Cancer 1 somestatus stop reason just information to hide Not Available Not Yet Recruiting Treatment Conditioning / Haploidentical Stem Cell Transplantation 1 somestatus stop reason just information to hide
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
Form Route Strength Solution Intravenous 23.30 mg Injection, solution, concentrate Intravenous 2 mg/ml Solution Intravenous 20 mg Solution Parenteral 20.000 mg Injection, solution, concentrate Intravenous Injection, solution Intravenous Injection, solution Intravenous 2 mg/1mL Injection, solution, concentrate Intravenous 2 mg/1mL Injection, solution, concentrate Intravenous; Parenteral 2 MG/ML Injection Intravenous 2 mg/ml Solution Intravenous Solution Intravenous 2 mg / mL Injection, solution, concentrate Intravenous 10 mg/5ml Injection, solution, concentrate Intravenous 20 mg/10ml Injection, solution Intravenous 20 mg/10mL Injection, solution Intravenous 25 mg/12.5mL Injection, solution Intravenous 30 mg/15mL Liquid Intravenous 2 mg / mL Injection, solution, concentrate Intravenous; Parenteral 10 MG Injection, solution, concentrate Intravenous; Parenteral 20 MG Injection, solution, concentrate Intravenous; Parenteral 25 MG Injection, solution, concentrate Intravenous; Parenteral 30 MG Solution Intravenous 2 mg/1ml - Prices
Unit description Cost Unit Novantrone 2 mg/ml Concentrate 10ml Vial 1649.32USD vial Novantrone 2 mg/ml vial 158.59USD ml Mitoxantrone 20 mg/10 ml vial 42.0USD ml Mitoxantrone 25 mg/12.5 ml vial 37.5USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source logP -3.1 Not Available - Predicted Properties
Property Value Source Water Solubility 0.734 mg/mL ALOGPS logP 0.91 ALOGPS logP 0.65 Chemaxon logS -2.8 ALOGPS pKa (Strongest Acidic) 8.27 Chemaxon pKa (Strongest Basic) 9.36 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 8 Chemaxon Polar Surface Area 163.18 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 123.53 m3·mol-1 Chemaxon Polarizability 48.49 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.7557 Blood Brain Barrier - 0.7979 Caco-2 permeable - 0.8957 P-glycoprotein substrate Substrate 0.8417 P-glycoprotein inhibitor I Non-inhibitor 0.8674 P-glycoprotein inhibitor II Non-inhibitor 0.8381 Renal organic cation transporter Non-inhibitor 0.7735 CYP450 2C9 substrate Non-substrate 0.7907 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.7013 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.8544 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9211 Ames test AMES toxic 0.9108 Carcinogenicity Non-carcinogens 0.8742 Biodegradation Not ready biodegradable 0.9727 Rat acute toxicity 2.3061 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.5839 hERG inhibition (predictor II) Inhibitor 0.6894
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 231.7285231 predictedDarkChem Lite v0.1.0 [M-H]- 203.87534 predictedDeepCCS 1.0 (2019) [M+H]+ 231.4031231 predictedDarkChem Lite v0.1.0 [M+H]+ 206.23335 predictedDeepCCS 1.0 (2019) [M+Na]+ 231.4222231 predictedDarkChem Lite v0.1.0 [M+Na]+ 213.28883 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation
- Specific Function
- ATP binding
- Gene Name
- TOP2B
- Uniprot ID
- Q02880
- Uniprot Name
- DNA topoisomerase 2-beta
- Molecular Weight
- 183265.825 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Yes
Intercalation
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (PubMed:17567603, PubMed:18790802, PubMed:22013166, PubMed:22323612). May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity)
- Specific Function
- ATP binding
- Gene Name
- TOP2A
- Uniprot ID
- P11388
- Uniprot Name
- DNA topoisomerase 2-alpha
- Molecular Weight
- 174383.88 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:15258110, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:15258110, PubMed:20972997). Exhibits catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2- and 4-hydroxy E1 and E2. Displays a predominant hydroxylase activity toward E2 at the C-4 position (PubMed:11555828, PubMed:12865317). Metabolizes testosterone and progesterone to B or D ring hydroxylated metabolites (PubMed:10426814). May act as a major enzyme for all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376, PubMed:15258110). Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and 14,15- EpETrE, that function as lipid mediators in the vascular system (PubMed:20972997). Additionally, displays dehydratase activity toward oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This activity is independent of cytochrome P450 reductase, NADPH, and O2 (PubMed:21068195). Also involved in the oxidative metabolism of xenobiotics, particularly converting polycyclic aromatic hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-damaging products (PubMed:10426814). Plays an important role in retinal vascular development. Under hyperoxic O2 conditions, promotes retinal angiogenesis and capillary morphogenesis, likely by metabolizing the oxygenated products generated during the oxidative stress. Also, contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression (By similarity)
- Specific Function
- aromatase activity
- Gene Name
- CYP1B1
- Uniprot ID
- Q16678
- Uniprot Name
- Cytochrome P450 1B1
- Molecular Weight
- 60845.33 Da
References
- Rochat B, Morsman JM, Murray GI, Figg WD, McLeod HL: Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001 Feb;296(2):537-41. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Rossato LG, Costa VM, de Pinho PG, Arbo MD, de Freitas V, Vilain L, de Lourdes Bastos M, Palmeira C, Remiao F: The metabolic profile of mitoxantrone and its relation with mitoxantrone-induced cardiotoxicity. Arch Toxicol. 2013 Oct;87(10):1809-20. doi: 10.1007/s00204-013-1040-6. Epub 2013 Apr 2. [Article]
- FDA Approved Drug Products: Mitoxantrone [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthezing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC1
- Uniprot ID
- P33527
- Uniprot Name
- Multidrug resistance-associated protein 1
- Molecular Weight
- 171589.5 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
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Drug created at June 13, 2005 13:24 / Updated at October 11, 2024 18:19