Idarubicin

Biological Activity

Idarubicin prevents DNA from unwinding by interfering with the enzyme topoisomerase II. Idarubicin belongs to the family called antitumor antibiotics. Idarubicin inhibits the proliferation of NALM-6 cells with an IC50 of 12 nM. Idarubicin has significant cytotoxic activity against multicellular spheroids, comparable to the antiproliferative effects on monolayer cells. Idarubicin is currently combined with cytosine arabinoside as a first line treatment of acute myeloid leukemia. Idarubicin plus Decitabine and cytarabine has entered in a phase II clinical trial in the treatment of adult acute myeloid leukemia, and adult acute monoblastic leukemia, refractory anemia with excess blasts.

Product Citations

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  ACS Biomater Sci Eng. 2021 Dec 21.

  Strategies to Maximize Anthracycline Drug Loading in Albumin Microbubbles
  Idarubicin purchased from AbMole

Protocol (for reference only)

Cell Experiment
Cell lines	K562S and K562R cells
Preparation method	MTT assay K562S and K562R cells were cultured in a 96-well plate (SPL) at a density of 1 × 104 cells in 100 μL of medium per well and treated with the indicated concentration of Imatinib or the AGM130 compound for 72 h. To measure the cell viability, the EZ-Cytox Cell Viability Assay kit was used. Ten microliters of MTT reagent was evenly treated in each well and incubated at 37 ◦C and 5% CO2 for 6 h. At the end of the incubation, the MTT factors of incubated cells in the plate were measured at the 450 nm wavelength using an ELISA detector.
Concentrations	0~10 μM
Incubation time	72 h

Animal Experiment
Animal models	Imatinibresistant K562 cells xenograft model using BALB/c nude mice
Formulation	saline
Dosages	15 mg/kg
Administration	i.p.

Chemical Information

Molecular Weight	497.49
Formula	C26H27NO9
CAS Number	58957-92-9
Solubility (25°C)	DMSO 50 mg/mL
Storage	2-8°C, dry, protect from light, sealed

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Kim WS, et al. Leuk Res. 5'-OH-5-nitro-Indirubin oxime (AGM130), an Indirubin derivative, induces apoptosis of Imatinib-resistant chronic myeloid leukemia cells.

[2] Ravandi F, et al. Cancer. Prognostic significance of alterations in IDH enzyme isoforms in patients with AML treated with high-dose cytarabine and idarubicin.

[3] Cortes J, et al. Cancer. Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia.

[4] Mandelli F, et al. J Clin Oncol. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10.

[5] Strolin Benedetti M, et al. Xenobiotica. Stereoselectivity of idarubicin reduction in various animal species and humans.