Mitoxantrone hydrochloride
[CAS# 70476-82-3]

Identification

• Classification: API >> Antineoplastic agents >> Anti-tumor adjuvant
• Name: Mitoxantrone hydrochloride
• Synonyms: 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthraquinone dihydrochloride; Mitozantrone hydrochloride; Novantrone
• Molecular Formula: C₂₂H₂₈N₄O₆^.2(HCl);C₂₂H₃₀Cl₂N₄O₆
• Molecular Weight: 517.41
• CAS Registry Number: 70476-82-3
• EC Number: 274-619-1
• SMILES: C1=CC(=C2C(=C1NCCNCCO)C(=O)C3=C(C=CC(=C3C2=O)O)O)NCCNCCO.Cl.Cl

Properties

• Solubility: 78 mM (DMSO), <1 mg/mL (water)

Safety Data

• Hazard Symbols: GHS08 Danger
• Hazard Statements: H341-H360
• Precautionary Statements: P203-P280-P318-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Germ cell mutagenicity	Muta.	1B	H340
Reproductive toxicity	Repr.	1B	H360
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Lact.	-	H362
Acute toxicity	Acute Tox.	2	H310
Carcinogenicity	Carc.	1B	H350
Specific target organ toxicity - single exposure	STOT SE	1	H370
Acute toxicity	Acute Tox.	4	H332
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Acute toxicity	Acute Tox.	4	H312
Reproductive toxicity	Repr.	1A	H360
Eye irritation	Eye Irrit.	2	H319
Carcinogenicity	Carc.	2	H351
Reproductive toxicity	Repr.	2	H361
Germ cell mutagenicity	Muta.	2	H341

Discovory and Applicatios

Mitoxantrone hydrochloride, a synthetic anthracenedione derivative, was discovered in the 1970s during research aimed at developing novel anticancer agents. Scientists were investigating compounds with structural similarities to anthracyclines, known for their potent antitumor activity. Through systematic screening of anthracenedione derivatives, Mitoxantrone emerged as a promising candidate due to its unique chemical structure and remarkable cytotoxic properties against cancer cells. Its discovery marked a significant advancement in cancer chemotherapy, offering a new treatment option for various malignancies.

Mitoxantrone hydrochloride is approved for the treatment of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL). It exerts its cytotoxic effects by intercalating into DNA, inhibiting topoisomerase II activity, and inducing DNA damage, leading to cell death. Mitoxantrone is used in combination chemotherapy regimens for metastatic breast cancer, particularly in patients who have failed other treatments. It is often combined with other cytotoxic drugs, such as cyclophosphamide and fluorouracil, to improve treatment efficacy.

Mitoxantrone hydrochloride is approved for the treatment of aggressive relapsing-remitting multiple sclerosis (MS) and progressive forms of MS. It modulates the immune response by suppressing T-cell activation and proliferation, leading to a reduction in inflammation and neurologic disability progression. Mitoxantrone is used as a disease-modifying therapy to reduce the frequency of relapses, delay disease progression, and improve quality of life in patients with severe, refractory MS. It is administered intravenously in carefully monitored treatment cycles to minimize potential adverse effects.

Researchers are investigating the use of Mitoxantrone in combination with other agents, such as prednisone or docetaxel, for the treatment of advanced prostate cancer. These combination regimens aim to improve overall survival and symptom control in patients with hormone-refractory prostate cancer.Mitoxantrone is being studied as a conditioning regimen in bone marrow transplantation for hematologic malignancies and autoimmune diseases. It is used to suppress the recipient's immune system and prepare the bone marrow for transplantation, reducing the risk of rejection and graft-versus-host disease.

Mitoxantrone hydrochloride is utilized in palliative care to alleviate pain and improve quality of life in patients with advanced cancer. It may be used as a single agent or in combination with opioid analgesics to control pain that is refractory to other treatments.

References

1987. Mitoxantrone in the treatment of acute leukemia. Investigational New Drugs, 5(4).
DOI: 10.1007/bf00169980

1991. Refractory myelomatosis treated with mitoxantrone in combination with vincristine and prednisone (NOP-regimen): a phase II study. British Journal of Haematology, 77(1).
DOI: 10.1111/j.1365-2141.1991.tb07951.x

2024. Multiple drugs. Reactions Weekly, 2033(1).
DOI: 10.1007/s40278-024-71066-9