Mitoxantrone

Mitoxantrone

File:Mitoxantrone skeletal.svg
File:Mitoxantrone ball-and-stick.png
Clinical data
Trade names	Novantrone
AHFS/Drugs.com	Monograph
MedlinePlus	a608019
Routes of administration	Mainly intravenous
ATC code	L01DB07 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	n/a
Protein binding	78%
Metabolism	Hepatic (CYP2E1)
Elimination half-life	75 hours
Excretion	Renal
Identifiers
IUPAC name 1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino) ethylamino]-anthracene-9,10-dione
CAS Number	65271-80-9 checkY
PubChem CID	4212
IUPHAR/BPS	7242
DrugBank	DB01204 checkY
ChemSpider	4067 checkY
UNII	BZ114NVM5P
KEGG	D08224 checkY
ChEBI	CHEBI:50729 checkY
ChEMBL	ChEMBL58 checkY
PDB ligand	MIX (PDBe, RCSB PDB)
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C22H28N4O6
Molar mass	444.488 g·mol−1
3D model (JSmol)	Interactive image
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 checkY Key:KKZJGLLVHKMTCM-UHFFFAOYSA-N checkY
(verify)

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.

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

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.

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.

Mechanism of action

Mitoxantrone is a type II topoisomerase inhibitor; it disrupts DNA synthesis and DNA repair in both healthy cells and cancer cells by intercalation between DNA bases. It is also classified as an antibiotic.

File:4g0v mix.png

Human topoisomerase II beta in complex with DNA and mitoxantrone. PDB entry 4g0v. Detail showing mitoxantrone (spheres) intercalated with DNA.

See also

• Pixantrone, a mitoxantrone analogue under development
• Losoxantrone