生物活性

Idarubicin HCl is the hydrochloride form ofanthracycline analog idarubicin, an antitumor antibiotic, used to treat acutemyelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL). Idarubicin Hydrochloride is the hydrochloride salt preparation of Idarubicin, an anthracycline and an analog of daunorubicin. This compound has been reported to trigger apoptotic cell death via enhancement of Fas and caspase-3/caspase-7 expression. In experiments, where cells were exposed to Idarubicin, reactive oxygen species (ROS) were produced which induced DNA strand breaks and prevented DNA polymerase reaction. Idarubicin Hydrochloride is an inhibitor of Topo II α. Idarubicin Hydrochloride is also a substrate of CYP2D6 and CYP2C9.

Idarubicindemonstrated it is an inhibitor of CYP450 2D6 isoenzyme with an IC50 of 2.5μg/ml.[1]

Growthinhibition of idarubicin

Cytotoxicityof idarubicin

Thetrypanocidal activity of idarubicin[9]

Antiviral activity of idarubicin for enteroviruses

体外研究

体内研究

激酶实验

细胞实验

Cellline[5]

The MCF-7 breast tumor cell lines weremaintained as monolayers in DMEM supplemented with glutamine (0.292mg/ml),penicillin/streptomycin (0.5ml/100ml medium), 5% fetal bovine serum, and 5% definedbovine serum at 37 °C in an atmosphere containing 5% CO₂.

Cellproliferation and cell death

GrowthInhibition

The capacity of idarubicin to interferewith the growth of the MCF-7 breast tumor cells was determined using the MTTtetrazolium dye assay. Briefly, cells subcultured at a density of 1x10⁴cells/mlin 96-well microplates were incubated with various concentrations of idarubicinfor 2 h. Drug was aspirated, cells were washed with incubation medium, andpermitted to grow for an additional 72 h prior to determination of viable cellnumbers.

Cellkilling

The capacity of idarubicin to produce celldeath was determined by monitoring the decline in the number of cellsoriginally plated using trypan blue exclusion and cell counting. MCF-7 cellssubcultured at a density of 1.5x10⁴cells/ml in 25-cm² T flaskswere incubated with 0.5μM idarubicin for 2 h at 37 °C. Drug was aspirated and the cells werewashed with ice-cold phosphate-buffered saline (PBS, pH 7.4). Cells were released from ¯asks byincubation with trypsin (0.05 mg/ml)/EDTA (0.02 mg/ml) for 5 min at 37^oC,collected in ice-cold PBS (pH 7.4), and centrifuged at 4 °C. Cell pellets wereresuspended in 300 ll ice-cold PBS and aliquots were mixed with trypan blue.Cells were loaded on a hemocytometer and viable cell numbers determined (cellviability was assessed by exclusion of trypan blue dye).

动物实验

Rat Balloon Angioplasty Model and PerivascularDrug Delivery[3]

Balloon injury of the left common carotidartery was performed in Male Sprague-Dawley rats (300–350 g). Briefly, afterinduction of anesthesia with isoflurane, a 2F balloon catheter was insertedthrough the left external carotid artery into the common carotid artery,insufflated at 2atm of pressure, pulled back to the bifurcation, and repeated 3times. The external carotid artery was then ligated, and blood flow was resumedthrough the common and internal carotid arteries. Immediately afterre-establishment of flow, idarubicin (50mg) or DMSO (vehicle, final 0.1%)dissolved in 300 ml of 25% F127 pluronic gel was applied around the injured segmentof the carotid artery (5 animals in each group). The pluronic gel is abiodegradable polymer, which is soluble in water at 4 ^oC but becomesa gel when in contact with tissues at 37 ^oC. Rats were euthanized 14days after injury, and the injured segments of common carotid arteries werecollected and fixed in 4% paraformaldehyde overnight for embedding in paraffin.

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

[1] Colburn DE, Giles FJ, Oladovich D, Smith JA. In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004;9(3):217-221.
[2] Kuffel MJ AM. Comparative resistance of idarubicin, doxorubicin and their C-13 alcohol metabolites in human MDR1 transfected NIH-3T3 cells. Cancer Chemother Pharmacol. . 1995;36(3):223-226.
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体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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