Mitoxantrone

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Mitoxantrone
Mitoxantrone skeletal.svg
Mitoxantrone ball-and-stick.png
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 YesY
ATC code L01DB07
PubChem CID 4212
DrugBank DB01204
ChemSpider 4067 YesY
UNII BZ114NVM5P YesY
KEGG D08224 YesY
ChEBI CHEBI:50729 YesY
ChEMBL CHEMBL58 YesY
Chemical data
Formula C22H28N4O6 
Mol. mass 444.481 g/mol
 YesY (what is this?)  (verify)

Mitoxantrone (INN, BAN, USAN. Also known as Mitozantrone (is the generic name in Australia)) is an anthracenedione (not an anthracycline) antineoplastic agent.

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]

Human topoisomerase iibeta in complex with DNA and mitoxantrone. PDB entry 4g0v.[4] Detail showing mitoxantrone (spheres) intercalated with DNA.

Mitoxantrone is a type II topoisomerase inhibitor; it disrupts DNA synthesis and DNA repair in both healthy cells and cancer cells, by intercalation.[5] between the DNA bases.

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:[6]

Mitoxantrone syn.svg

See also[edit]

External links[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ Wu, C. -C.; Li, Y. -C.; Wang, Y. -R.; Li, T. -K.; Chan, N. -L. (2013). "On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs". Nucleic Acids Research 41 (22): 10630–10640. doi:10.1093/nar/gkt828. PMID 24038465.  edit
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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.