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{{Short description|Chemical compound}}
⚫ {{drugbox | verifiedrevid = 408764304
{{Drugbox
|
⚫ | verifiedrevid = 462252883
| IUPAC_name = 1,4-dihydroxy-5,8-bis-anthracene-9,10-dione | IUPAC_name = 1,4-dihydroxy-5,8-bis-anthracene-9,10-dione
| image = Mitoxantrone skeletal.svg | image = Mitoxantrone skeletal.svg
| image2 = Mitoxantrone ball-and-stick.png
⚫ | CASNo_Ref = {{cascite|correct|CAS}}
<!--Clinical data-->
| tradename = Novantrone
| Drugs.com = {{drugs.com|monograph|mitoxantrone-hydrochloride}}
| MedlinePlus = a608019
⚫ | pregnancy_US = D
⚫ | legal_status = Rx-only
⚫ | routes_of_administration = Mainly ]
<!--Pharmacokinetic data-->
⚫ | bioavailability = n/a
⚫ | protein_bound = 78%
⚫ | metabolism = ] (])
⚫ | elimination_half-life = 75 hours
⚫ | excretion = ]
<!--Identifiers-->
| IUPHAR_ligand = 7242
⚫ | CAS_number_Ref = {{cascite|correct|??}}
⚫ | CAS_number = 65271-80-9
⚫ | ATC_prefix = L01
⚫ | ATC_suffix = DB07
⚫ | PubChem = 4212
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
⚫ | DrugBank = DB01204
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4067 | ChemSpiderID = 4067
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = BZ114NVM5P | UNII = BZ114NVM5P
⚫ | KEGG_Ref = {{keggcite|correct|kegg}}
| InChI = 1/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
⚫ | KEGG = D08224
| InChIKey = KKZJGLLVHKMTCM-UHFFFAOYAS
| ChEBI_Ref = {{ebicite|correct|EBI}}
⚫ | smiles = O=C2c1c(c(NCCNCCO)ccc1NCCNCCO)C(=O)c3c2c(O)ccc3O
| ChEBI = 50729
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 58 | ChEMBL = 58
| PDB_ligand = MIX
<!--Chemical data-->
⚫ | C=22 | H=28 | N=4 | O=6
⚫ | SMILES = O=C2c1c(c(NCCNCCO)ccc1NCCNCCO)C(=O)c3c2c(O)ccc3O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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 | StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = KKZJGLLVHKMTCM-UHFFFAOYSA-N | StdInChIKey = KKZJGLLVHKMTCM-UHFFFAOYSA-N
⚫ | CAS_number = 65271-80-9
⚫ | ATC_prefix = L01
⚫ | ATC_suffix = DB07
⚫ | PubChem = 4212
⚫ | DrugBank = APRD00371
⚫ | KEGG_Ref = {{keggcite|correct|kegg}}
⚫ | KEGG = D08224
⚫ | C = 22 | H = 28 | N = 4 | O = 6
| molecular_weight = 444.481 ]/]
⚫ | bioavailability = n/a
⚫ | protein_bound = 78%
⚫ | metabolism = ] (])
⚫ | elimination_half-life = 75 hours
⚫ | excretion = ]
⚫ | pregnancy_US = D
⚫ | legal_status = Rx-only
⚫ | routes_of_administration = '''Exclusively''' ]
}} }}
'''Mitoxantrone''' is an anthracenedione (not an anthracycline) ] agent. '''Mitoxantrone''' (INN, BAN, USAN; also known as '''Mitozantrone''' in Australia; trade name '''Novantrone''') is an ] ] agent.


==Uses== ==Uses==
It is used in the treatment of certain types of cancer, mostly ] ], ], and ]. It was also shown to improve the survival of children suffering from first relapse of ].<ref name="Parker">{{cite journal |author=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 |title=Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial |journal=Lancet |volume= |issue= |pages= |year=2010 |pmid=21131038 |doi=10.1016/S0140-6736(10)62002-8}}</ref> Mitoxantrone is used to treat certain types of cancer, mostly ]. It improves the survival rate of children suffering from ] relapse.<ref name="Parker">{{cite journal | vauthors = 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 | display-authors = 6 | title = Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial | journal = Lancet | volume = 376 | issue = 9757 | pages = 2009–2017 | date = December 2010 | pmid = 21131038 | pmc = 3010035 | doi = 10.1016/S0140-6736(10)62002-8 }}</ref>

⚫ The combination of mitoxantrone and ] is approved as a second-line treatment for metastatic hormone-refractory ]. This combination has been the first line of treatment, until recently, when combination of ] and prednisone has been shown to improve survival and disease-free period.<ref>{{cite book |chapter=Cancer Chemotherapy |author=Katzung, Bertram G. |title=Basic and clinical pharmacology |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2006 |isbn=0-07-145153-6 |edition=10th |oclc=157011367}}</ref>


⚫ The combination of mitoxantrone and ] is approved as a second-line treatment for metastatic hormone-refractory ]. This combination was once the first line of treatment; however, a combination of ] and prednisone improves survival rates and lengthens the disease-free period.<ref>{{cite book |chapter=Cancer Chemotherapy | vauthors = Katzung BG |title=Basic and clinical pharmacology |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2006 |isbn=0-07-145153-6 |edition=10th |oclc=157011367}}</ref>
Mitoxantrone is also used to treat ] (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.<ref name="Fox">{{cite journal |author=Fox E |title=Management of worsening multiple sclerosis with mitoxantrone: a review |journal=Clin Ther |volume=28 |issue=4 |pages=461–74 |year=2006 |pmid=16750460 |doi=10.1016/j.clinthera.2006.04.013}}</ref> Mitoxantrone is also used to treat ] (MS), most notably the ] 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.<ref name="Fox">{{cite journal | vauthors = Fox EJ | title = Management of worsening multiple sclerosis with mitoxantrone: a review | journal = Clinical Therapeutics | volume = 28 | issue = 4 | pages = 461–474 | date = April 2006 | pmid = 16750460 | doi = 10.1016/j.clinthera.2006.04.013 }}</ref>

⚫ ==Mechanism of action==

Mitoxantrone is a ] ]; it disrupts ] and ] in both healthy cells and cancer cells.

It also engages in ].<ref name="pmid">{{cite journal |author=Mazerski J, Martelli S, Borowski E |title=The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations |journal=Acta Biochim. Pol. |volume=45 |issue=1 |pages=1–11 |year=1998 |pmid= 9701490|doi= |url=}}</ref>


==Side effects== ==Side effects==
As other drugs in its class, mitoxantrone may cause several ]s of varying severity, such as ], ], ], heart damage, and ]. Some side effects may have delayed onset. ] is a particularly concerning effect as it is irreversible; regular monitoring with ]s or ]s is recommended for people taking mitoxantrone. Mitoxantrone, as with other drugs in its class, may cause ] of varying severity, including ], ], ], heart damage and ], possibly with delayed onset. ] is a particularly concerning effect as it is irreversible; thus regular monitoring with ]s or ]s 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.<ref name="FDA Postmarket Drug Safety">{{cite web|title=Mitoxantrone Hydrochloride (marketed as Novantrone and generics) – Healthcare Professional Sheet text version|url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126445.htm|publisher=U.S. Food and Drug Administration|access-date=19 September 2014|ref=fdapostmarket}}</ref>
The medication carries a total lifetime dose based on body surface area.<ref name="Fox"/>


⚫ ==Mechanism of action==
==Synthesis==
Mitoxantrone is a ] ]; it disrupts ] and ] in both healthy cells and cancer cells by ]<ref name="pmid">{{cite journal | vauthors = Mazerski J, Martelli S, Borowski E | title = The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations | journal = Acta Biochimica Polonica | volume = 45 | issue = 1 | pages = 1–11 | year = 1998 | pmid = 9701490 | doi = 10.18388/abp.1998_4280 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kapuscinski J, Darzynkiewicz Z | title = Interactions of antitumor agents Ametantrone and Mitoxantrone (Novatrone) with double-stranded DNA | journal = Biochemical Pharmacology | volume = 34 | issue = 24 | pages = 4203–4213 | date = December 1985 | pmid = 4074383 | doi = 10.1016/0006-2952(85)90275-8 }}</ref> between DNA bases. It is also classified as an antibiotic.<ref>{{Cite web | url=https://livertox.nlm.nih.gov/Mitoxantrone.htm | title=Mitoxantrone}}</ref>
]
]

{{Cite journal|doi=10.1021/jm00195a002|title=Antitumor agents. 1. 1,4-Bis-9,10-anthracenediones|pmid=490545|year=1979|last1=Murdock|first1=K. C.|last2=Child|first2=R. G.|last3=Fabio|first3=P. F.|last4=Angier|first4=Robert D.|last5=Wallace|first5=Roslyn E.|last6=Durr|first6=Frederick E.|last7=Citarella|first7=R. V.|journal=Journal of Medicinal Chemistry|volume=22|issue=9|pages=1024}}


==See also== == See also ==
*], a mitoxantrone ] under development * ], a mitoxantrone ] under development
* ]
* Naphtoquinoxalinediones, potential antitumorals, obtained from diamino-1,2 anthraquinones using a regioselective synthesis.<ref>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., 62, 3, 526-530.</ref>
*]
*]


==References== == References ==
{{Reflist}} {{Reflist}}


== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/mitoxantrone | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Mitoxantrone }}

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