Idarubicin hydrochloride
[CAS# 57852-57-0]

Identification

• Classification: API >> Antineoplastic agents >> Antibiotic antineoplastic agents
• Name: Idarubicin hydrochloride
• Synonyms: (7S-cis)-9-Acetyl-7-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11-trihydroxy-5,12-naphthacenedione hydrochloride
• Molecular Formula: C₂₆H₂₇NO₉.HCl
• Molecular Weight: 533.95
• CAS Registry Number: 57852-57-0
• EC Number: 260-990-7
• SMILES: C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](CC3=C2C(=C4C(=C3O)C(=O)C5=CC=CC=C5C4=O)O)(C(=O)C)O)N)O.Cl

Properties

• Solubility: 100 mg/mL (DMSO), 100 mg/mL (ethanol) (Expl.)

Safety Data

• Hazard Symbols: GHS06;GHS08 Dander
• Risk Statements: H300-H341-H351-H360
• Safety Statements: P203-P264-P270-P280-P301+P316-P318-P321-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	2	H300
Reproductive toxicity	Repr.	1B	H360
Carcinogenicity	Carc.	2	H351
Germ cell mutagenicity	Muta.	2	H341
Germ cell mutagenicity	Muta.	1B	H340
Carcinogenicity	Carc.	1A	H350
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	3	H311
Reproductive toxicity	Repr.	2	H361
Carcinogenicity	Carc.	1B	H350

• Transport Information: UN 2811

Discovery and Applications

Idarubicin hydrochloride is an anthracycline chemotherapy drug derived from daunorubicin, which itself is a natural product of *Streptomyces peucetius*. It was first synthesized in the 1980s by scientists looking to improve upon the efficacy of daunorubicin while reducing its side effects, particularly cardiotoxicity. Idarubicin shares the same mechanism of action as other anthracyclines, intercalating into DNA to inhibit topoisomerase II, an enzyme necessary for DNA replication and repair. This action prevents the replication of cancer cells, leading to cell death. The drug is particularly used in the treatment of acute leukemia and other hematologic malignancies.

Idarubicin hydrochloride's chemical structure is similar to that of daunorubicin, with a modification in the sugar moiety, making it more lipophilic. This structural change allows idarubicin to better penetrate the cell membrane and reach its target in tumor cells. It is administered intravenously and is commonly used in the treatment of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), especially in combination with other chemotherapy agents. In addition to leukemia, idarubicin is sometimes used in the treatment of non-Hodgkin’s lymphoma and other cancers that respond to anthracyclines.

Idarubicin’s main advantage over daunorubicin is its higher potency in killing cancer cells, which makes it effective in treating cancers like leukemia. It is often included in combination chemotherapy regimens, such as the “7+3” regimen, which combines idarubicin with cytarabine for the treatment of AML. This regimen has been the standard treatment for newly diagnosed AML patients and has significantly improved survival rates. Idarubicin is also used in treating relapsed or refractory leukemia, where it may provide additional efficacy in cases where other treatments have failed.

Despite its effectiveness, idarubicin shares some of the common side effects seen with other anthracyclines, including nausea, vomiting, hair loss, and myelosuppression (bone marrow suppression). The suppression of bone marrow can result in a decreased production of blood cells, which increases the risk of infections, anemia, and bleeding. One of the most serious concerns with idarubicin, as with other anthracyclines, is cardiotoxicity. This can lead to heart damage, especially with prolonged use or high doses. To mitigate these risks, careful monitoring of heart function is required during treatment, and the drug is generally used with caution in patients with pre-existing heart conditions.

Research into improving the therapeutic index of idarubicin is ongoing. Strategies such as liposomal formulations and conjugation with targeted delivery systems are being explored to enhance the drug’s efficacy in tumor tissues while minimizing damage to healthy cells. These innovations aim to reduce the drug’s side effects and improve patient outcomes.

In conclusion, idarubicin hydrochloride is a potent chemotherapy agent that has become a mainstay in the treatment of acute leukemia. Its ability to effectively kill cancer cells while maintaining a relatively high degree of specificity for tumor tissues makes it an essential component of modern chemotherapy regimens for hematologic cancers. Despite its challenges, including the risk of cardiotoxicity and bone marrow suppression, idarubicin continues to be a valuable tool in oncology.

References

1984. Total chemical synthesis and antitumor evaluation of 4-demethoxy-10,10-dimethyldaunomycin. Journal of Medicinal Chemistry, 27(10).
DOI: 10.1021/jm00376a021

1987. Pharmacokinetics of idarubicin after daily intravenous administration in leukemic patients. Leukemia Research, 11(1).
DOI: 10.1016/0145-2126(87)90113-5

1994. Modulation of anthracycline accumulation and metabolism in rat hepatocytes in culture by three revertants of multidrug resistance. Cancer Chemotherapy and Pharmacology, 34(6).
DOI: 10.1007/bf00686284"