57852-57-0 Usage
Description
Idarubicin hydrochloride, also known as Idamycin, is a derivative of daunorubicin, an anthracycline antibiotic. It is a DNA topoisomerase II (topo II) inhibitor and is available in 5-, 10-, and 20-mL vials for intravenous (IV) administration. Idarubicin hydrochloride is characterized by its orange solid appearance and is marketed under the brand name Zavedos. It is less cardiotoxic than doxorubicin, has milder side effects, and is more potent in experimental leukemias. Idarubicin hydrochloride is also active in daunorubicin-resistant patients and has shown activity against breast cancer, Hodgkin's and non-Hodgkin's lymphoma.
Uses
1. Used in Oncology:
Idarubicin hydrochloride is used as an antineoplastic agent for the treatment of acute myeloid leukemia (AML), acute nonlymphocytic leukemia, and acute lymphocytic leukemia. It is particularly effective due to its fast distributive phase, high volume of distribution, and its ability to bind to tissue, resulting in higher concentrations in blood and bone marrow cells compared to plasma.
2. Used in Drug Resistance:
Idarubicin hydrochloride is used as a treatment option for patients who are resistant to daunorubicin, offering an alternative for those who do not respond well to the initial treatment.
3. Used in Cardiotoxicity Reduction:
Idarubicin hydrochloride is used as a less cardiotoxic alternative to doxorubicin, making it a preferred choice for patients with a higher risk of developing cardiac issues.
4. Used in Experimental Cancer Treatments:
Idarubicin hydrochloride is used as a topo II inhibitor for MCF-7 cells, with an IC50 of 3.3 ng/mL, indicating its potency in experimental cancer treatments.
5. Used in Oral Administration:
Idarubicin hydrochloride is an orally active anthracycline, providing an alternative route of administration for patients who may not be suitable candidates for IV treatment.
6. Used in Leukemia Treatment:
Idarubicin hydrochloride is used as a primary treatment for various types of leukemia, including AML and acute lymphocytic leukemia, due to its high efficacy and lower incidence of cardiotoxicity compared to other anthracyclines.
7. Used in Cancer Treatment for Specific Cancer Types:
Idarubicin hydrochloride is used in the treatment of breast cancer, Hodgkin's lymphoma, and non-Hodgkin's lymphoma, demonstrating its versatility in addressing different types of cancer.
Originator
Erbamont (Italy)
Mechanism of action
Increased rates of remission have been noted with the use of idarubicin compared to other anthracyclines antineoplastic agents. Unlike its congeners, idarubicin shows significant oral bioavailability and is lipophilic enough to penetrate the blood-brain barrier. Currently, however, it is given only by the IV route and is not used in the treatment of brain cancer.
Clinical Use
Its primary indication is in acute myeloid leukemia, and it is
administered in combination with other antileukemic drug.
Safety Profile
A poison by ingestion,
subcutaneous, intravenous, and
intraperitoneal routes. When heated to
decomposition it emits toxic vapors of NOx,
HCl, and Cl-.
Drug interactions
Potentially hazardous interactions with other drugs
Other myelosuppressant medication and
radiotherapy: increased risk of myelosuppression.
Antipsychotics: avoid concomitant use with
clozapine, increased risk of agranulocytosis.
Ciclosporin: concentration increased by ciclosporin.
Cytotoxics: possible increased cardiotoxicity with
trastuzumab.
Live vaccines: risk of generalised infections - avoid.
Metabolism
Idarubicin is reduced by aldoketoreductases to idarubicinol, which is as active as the parent drug. Because there is no aromatic methoxy group, there is no O-dealkylation to the C4-phenol. The major metabolite is free, unconjugated idarubicinol. The half-lives of both idarubicin and idarubicinol are 22 and 45 hours, respectively. Idarubicin is administered IV at a dose of 10 to 12 mg/m2 /day for 3 to 4 days, and the idarubicinol metabolite can still be found in therapeutic concentrations in the blood 8 days after administration. Like other anthracyclines, excretion primarily is fecal, with a lesser dependence on renal elimination.
references
[1] h. dorota halicka, m. fevzi ozkaynak, oya levendoglu-tugal, claudio sandoval , karen seiter, malgorzata kajstura, frank traganos, somasunadaram jayabose, and zbigniew darzynkiewicz. dna damage response as a biomarker in treatment of leukemias. cell cycle. 2009, 8(11): 1720–1724.[2] haydar ?elik and emel arin?. evaluation of the protective effects of quercetin, rutin, resveratrol, naringenin and trolox against idarubicin-induced dna damage. j pharm pharmaceut sci. 2010, 13(2): 231 – 241.[3] ching-hon pui, siebold s. n. de graaf, lois w. dow, john h. rodman, william e. evans, bruce s. alpert and sharon b. murphy. phase i clinical trial of orally administered 4-demethoxydaunorubicin (idarubicin) with pharmacokinetic and in vitro drug sensitivity testing in children with refractory leukemia. cancer research. 1988, 48: 5348-5352.
Check Digit Verification of cas no
The CAS Registry Mumber 57852-57-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,7,8,5 and 2 respectively; the second part has 2 digits, 5 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 57852-57:
(7*5)+(6*7)+(5*8)+(4*5)+(3*2)+(2*5)+(1*7)=160
160 % 10 = 0
So 57852-57-0 is a valid CAS Registry Number.
InChI:InChI=1/C26H27NO9.ClH/c1-10-21(29)15(27)7-17(35-10)36-16-9-26(34,11(2)28)8-14-18(16)25(33)20-19(24(14)32)22(30)12-5-3-4-6-13(12)23(20)31;/h3-6,10,15-17,21,29,32-34H,7-9,27H2,1-2H3;1H/t10-,15-,16-,17-,21+,26-;/m0./s1
57852-57-0Relevant articles and documents
Novel idarubicin hydrochloride compound
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Paragraph 0128-0129, (2020/03/12)
Disclosed is a novel idarubicin hydrochloride omega-type compound. The novel idarubicin hydrochloride omega-type compound has low hygroscopicity and high storage stability, is beneficial to drug quality control and the like, and is applicable to preparation of drugs for treating or preventing acute leukemia, advanced breast cancer, diffuse large B cell lymphoma of central nervous systems, non-Hodgkin's lymphoma, myelodysplastic syndrome, lung cancer, melanoma, soft tissue sarcoma, multiple myeloma, liver cancer, colorectal cancer, kidney cancer, prostate cancer, endometrial cancer, testiculartumor, ovarian cancer, head and neck cancer, and the like.
CRYSTALLIZATION OF IDARUBICIN HYDROCHLORIDE
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Paragraph 0091, (2014/08/19)
A method is provided for production of crystalline idarubicin hydrochloride, the method including the steps of: (i) producing a mixture containing (a) idarubicin hydrochloride, (b) at least one alcohol selected from 1-butanol, 2-butanol, and 1-pentanol, and (c) water; and (ii) crystallizing idarubicin hydrochloride from this mixture. A crystalline idarubicin hydrochloride is also provided characterized by a powder x-ray diffraction pattern in which at least reflexes at diffraction angles occur in the following ranges (in 2Θ): 7.2-7.7; 11.7-12.2; 16.2-16.7; 16.7-17.2; 19.6-20.1; 19.8-20.3; 22.2-22.7, and 22.9-23.4.
Method of preparing 4-R-substituted 4-demethoxydaunorubicin
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Page 4, (2008/06/13)
A method of synthesizing 4-R-substituted anthracyclines and their corresponding salts from 4-demethyldaunorubicin includes the steps of treating 4-demethyldaunorubicin with a sulfonylating agent to form 4-demethyl-4-sulfonyl-R3-daunorubicin. 4-Demethyl-4-R3-sulfonyl-daunorubicin is then subject to a reducing agent in the presence of a transition metal catalyst in a temperature range of about 30° C. to about 100° C. in a polar aprotic solvent in an inert atmosphere. Protected 4-demethoxy-4-R-daunomycin then undergoes hydrolysis in a basic solution to form the 4-R-substituted anthracyclines. The novel method lacks the step of forming a stereospecific glycoside bond between aglycone and aminoglycoside. The method also increases the yield of the final product up to 30 to 40%.
