Mitoxantrone

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Mitoxantrone
Mitoxantrone skeletal.svg
Mitoxantrone ball-and-stick.png
Clinical data
Trade namesNovantrone
AHFS/Drugs.comMonograph
MedlinePlusa608019
Routes of
administration
Mainly intravenous
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailabilityn/a
Protein binding78%
MetabolismHepatic (CYP2E1)
Elimination half-life75 hours
ExcretionRenal
Identifiers
  • 1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)
    ethylamino]-anthracene-9,10-dione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC22H28N4O6
Molar mass444.488 g·mol−1
3D model (JSmol)
  • O=C2c1c(c(NCCNCCO)ccc1NCCNCCO)C(=O)c3c2c(O)ccc3O
  • 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 checkY
  • Key:KKZJGLLVHKMTCM-UHFFFAOYSA-N checkY
  

Mitoxantrone (INN, BAN, USAN; also known as Mitozantrone in Australia; trade name Novantrone) is an anthracenedione antineoplastic agent.

Uses[]

Mitoxantrone is used to treat certain types of cancer, mostly acute myeloid leukemia. It improves the survival rate of children suffering from acute lymphoblastic leukemia relapse.[1]

The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer. Until recently this combination was the first line of treatment; however, a combination of docetaxel and prednisone improves survival rates and lengthens the disease-free period.[2]

Mitoxantrone is also used to treat multiple sclerosis (MS), most notably the subset of the disease known as secondary-progressive MS. In the absence of a cure, mitoxantrone is effective in slowing the progression of secondary-progressive MS and extending the time between relapses in both relapsing-remitting MS and progressive-relapsing MS.[3]

Side effects[]

Mitoxantrone, as with other drugs in its class, may cause adverse reactions of varying severity, including nausea, vomiting, hair loss, heart damage and immunosuppression, possibly with delayed onset. Cardiomyopathy is a particularly concerning effect as it is irreversible; thus regular monitoring with echocardiograms or MUGA scans is recommended for patients.

Because of the risk of cardiomyopathy, mitoxantrone carries a limit on the cumulative lifetime dose (based on body surface area) in MS patients.[4]

Mechanism of action[]

Human topoisomerase II beta in complex with DNA and mitoxantrone. PDB entry 4g0v.[5] 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[6][7] between DNA bases. It is also classified as an antibiotic.[8]

See also[]

  • Pixantrone, a mitoxantrone analogue under development
  • Losoxantrone

References[]

  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. ^ 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. ^ "Mitoxantrone Hydrochloride (marketed as Novantrone and generics) – Healthcare Professional Sheet text version". U.S. Food and Drug Administration. Retrieved 19 September 2014.
  5. ^ 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. PMC 3905874. PMID 24038465.
  6. ^ 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. doi:10.18388/abp.1998_4280. PMID 9701490.
  7. ^ Kapuscinski, J; Darzynkiewicz, Z (1985). "Interactions of antitumor agents Ametantrone and Mitoxantrone (Novatrone) with double-stranded DNA". Biochem Pharmacol. 34 (24): 4203–13. doi:10.1016/0006-2952(85)90275-8. PMID 4074383.
  8. ^ "Mitoxantrone".

External links[]

  • "Mitoxantrone". Drug Information Portal. U.S. National Library of Medicine.
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