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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/23 01:54:59」(JST)
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Mitoxantrone
|
| Systematic (IUPAC) name |
1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)
ethylamino]-anthracene-9,10-dione |
| Clinical data |
| Trade names |
Novantrone |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a608019 |
| Pregnancy cat. |
D (US) |
| Legal status |
℞ Prescription only |
| Routes |
Mainly intravenous |
| Pharmacokinetic data |
| Bioavailability |
n/a |
| Protein binding |
78% |
| Metabolism |
Hepatic (CYP2E1) |
| Half-life |
75 hours |
| Excretion |
Renal |
| Identifiers |
| CAS number |
65271-80-9 Y |
| ATC code |
L01DB07 |
| PubChem |
CID 4212 |
| DrugBank |
DB01204 |
| ChemSpider |
4067 Y |
| UNII |
BZ114NVM5P Y |
| KEGG |
D08224 Y |
| ChEBI |
CHEBI:50729 Y |
| ChEMBL |
CHEMBL58 Y |
| Chemical data |
| Formula |
C22H28N4O6 |
| Mol. mass |
444.481 g/mol |
SMILES
- O=C2c1c(c(NCCNCCO)ccc1NCCNCCO)C(=O)c3c2c(O)ccc3O
|
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 Y
Key:KKZJGLLVHKMTCM-UHFFFAOYSA-N Y
|
Y (what is this?) (verify)
|
Mitoxantrone is an anthracenedione (not an anthracycline) antineoplastic agent.
Contents
- 1 Uses
- 2 Mechanism of action
- 3 Side effects
- 4 Synthesis
- 5 See also
- 6 References
Uses[edit]
It is used in the treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. It was also shown to improve the survival of children suffering from first relapse of acute lymphoblastic leukaemia.[1]
The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer. This combination has been the first line of treatment, until recently, when combination of docetaxel and prednisone has been shown to improve survival and disease-free period.[2]
Mitoxantrone is also used to treat multiple sclerosis (MS), most notably the subset known as secondary progressive MS. Mitoxantrone will not cure multiple sclerosis, but is effective in slowing the progression of secondary progressive MS and extending the time between relapses in relapsing-remitting MS and progressive relapsing MS.[3]
Mechanism of action[edit]
Mitoxantrone is a type II topoisomerase inhibitor; it disrupts DNA synthesis and DNA repair in both healthy cells and cancer cells.
It also engages in intercalation.[4]
Side effects[edit]
As other drugs in its class, mitoxantrone may cause several adverse reactions of varying severity, such as nausea, vomiting, hair loss, heart damage, and immunosuppression. Some side effects may have delayed onset. Cardiomyopathy is a particularly concerning effect as it is irreversible; regular monitoring with echocardiograms or MUGA scans is recommended for people taking mitoxantrone.
The medication carries a total lifetime dose based on body surface area.[3]
Synthesis[edit]
Mitoxantrone can be prepared from quinizarin:[5]
See also[edit]
- Pixantrone, a mitoxantrone analogue under development
- Naphtoquinoxalinediones, potential antitumorals, obtained from diamino-1,2 anthraquinones using a regioselective synthesis.[6]
- ametantrone
- piroxantrone
References[edit]
- ^ Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Révész T, Darbyshire P, Love S, Saha V (2010). "Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial". Lancet 376 (9757): 2009–2017. doi:10.1016/S0140-6736(10)62002-8. PMC 3010035. PMID 21131038.
- ^ Katzung, Bertram G. (2006). "Cancer Chemotherapy". Basic and clinical pharmacology (10th ed.). New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-145153-6. OCLC 157011367.
- ^ a b Fox E (2006). "Management of worsening multiple sclerosis with mitoxantrone: a review". Clin Ther 28 (4): 461–74. doi:10.1016/j.clinthera.2006.04.013. PMID 16750460.
- ^ Mazerski J, Martelli S, Borowski E (1998). "The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations". Acta Biochim. Pol. 45 (1): 1–11. PMID 9701490.
- ^ Murdock, K. C.; Child, R. G.; Fabio, P. F.; Angier, Robert D.; Wallace, Roslyn E.; Durr, Frederick E.; Citarella, R. V. (1979). "Antitumor agents. 1. 1,4-Bis[(aminoalkyl)amino]-9,10-anthracenediones". Journal of Medicinal Chemistry 22 (9): 1024. doi:10.1021/jm00195a002. PMID 490545.
- ^ Baron M, Giorgi-Renault S, Renault J, et al. (1984). "Heterocycles with a quinone function.5.An abnormal reaction of butanedione with 1,2-diaminoanthraquinone - Crystalline structure obtained from naphto(2,3-f) quinoxaline-7,12 dione". Can. J. Chem. (in French) 62 (3): 526–530. doi:10.1139/v84-087.
English Journal
- The metabolic profile of mitoxantrone and its relation with mitoxantrone-induced cardiotoxicity.
- Rossato LG, Costa VM, de Pinho PG, Arbo MD, de Freitas V, Vilain L, de Lourdes Bastos M, Palmeira C, Remião F.SourceREQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, Porto, 4050-313, Portugal, luciana.g.rossato@gmail.com.
- Archives of toxicology.Arch Toxicol.2013 Apr 2. [Epub ahead of print]
- Mitoxantrone (MTX) is an antitumor agent that causes cardiotoxicity in 18 % patients. The metabolic profile of MTX was assessed after incubation of 100 μM MTX with hepatic S9 fraction isolated from rats. The presence of MTX and its metabolites was also assessed in vivo through the analysis of liv
- PMID 23545721
- Magnetic drug targeting reduces the chemotherapeutic burden on circulating leukocytes.
- Janko C, Dürr S, Munoz LE, Lyer S, Chaurio R, Tietze R, Löhneysen Sv, Schorn C, Herrmann M, Alexiou C.SourceDepartment of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, Erlangen 91054, Germany. stephan.duerr@uk-erlangen.de.
- International journal of molecular sciences.Int J Mol Sci.2013 Apr 2;14(4):7341-55. doi: 10.3390/ijms14047341.
- Magnetic drug targeting (MDT) improves the integrity of healthy tissues and cells during treatment with cytotoxic drugs. An anticancer drug is bound to superparamagnetic iron oxide nanoparticles (SPION), injected into the vascular supply of the tumor and directed into the tumor by means of an extern
- PMID 23549268
- Engineering porous silicon nanostructures as tunable carriers for mitoxantrone dihydrochloride.
- Tzur-Balter A, Gilert A, Massad-Ivanir N, Segal E.SourceThe Interdepartmental Program of Biotechnology, Technion - Israel Institute of Technology, Haifa 32000, Israel.
- Acta biomaterialia.Acta Biomater.2013 Apr;9(4):6208-17. doi: 10.1016/j.actbio.2012.12.010. Epub 2012 Dec 27.
- Nanostructured porous silicon (PSi) thin films, fabricated by the electrochemical anodization of single crystalline Si wafers, are studied as delivery systems for the anticancer drug mitoxantrone dihydrochloride (MTX). The surface chemistry of the PSi carriers was tailored by surface alkylation usin
- PMID 23274152
Japanese Journal
- 自家骨髄移植を併用した大量化学療法で完全寛解を得た治療抵抗性ろ胞性リンパ腫
- A phase II trial of prednisone, oral etoposide, and novantrone (PEN) as initial treatment of non-Hodgkin's lymphoma in elderly patients
- Caffeine reverses the cytotoxic and cell kinetic effects of Novantrone(mitoxantrone)
Related Links
- Learn about the prescription medication Novantrone (Mitoxantrone for Injection Concentrate), drug uses, dosage, side effects, drug interactions, warnings, reviews and patient labeling.
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