Idarubicin HCl

Administered via i.v.

NALM-6 cells

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.

Idarubicin HCl (Idamycin, Zavedos, 4-demethoxydaunorubicin) is a hydrochloride salt form of Idarubicin which is an anthracycline antibiotic and a DNA topoisomerase II (topo II) inhibitor for MCF-7 cells with an IC50 of 3.3 ng/mL.

Idarubicin is a substrate for CYP450 2D6 and 2C9.

3.3 ng/mL, 3.3 ng/mL, 3.3 ng/mL, 3.3 ng/mL, 3.3 ng/mL, 3.3 ng/mL

Reduction of Idarubicin is dependent upon ketone reductases, and proceeds more stereoselectively than that of most ketones giving rise to the (13S)-epimer almost exclusively. The high stereospecificity in Idarubicin reduction might result from chiral induction due to the presence of asymmetric centres near to the carbonyl group in Idarubicin. [7]

[5], CYP450 metabolism experiments, Evaluation of Idarubicin metabolism by the CYP450 isoenzymes 3A4, 2D6, 2C8, 2C9, and 1A2 is completed using isolated human CYP450 proteins for each isoform. The high throughput P450 inhibition testing method is utilized for these evaluations. The metabolism experiments are designed to investigate the following properties of each drug: (1) if Idarubicin is a substrate of the CYP450 3A4, 2C8, 2C9, 1A2 or 2D6 isoenzymes, (2) if metabolism is affected by known inhibitors of each isoenzyme, (3) if Idarubicin is inhibitors of CYP450 isoenzymes, and (4) if caspofungin or itraconazole inhibit the CYP450 metabolism of Idarubicin. Dibenzylfluorescein (DBF) (CYP3A4, CYP2C8, CYP2C9), 3-cyano-7-ethoxycoumarin (Cyp1A2), and 7-methoxy-4-(aminomethyl)-coumarin (MAMC) (CYP2D6) are the known substrates utilized as controls to confirm the respective isoenzyme activity and evaluate the effects of Idarubicin on the isoenzyme activity. In addition, ketoconazole, quercetin, suflaphenazole, furafylline, and quinidine are utilized as control CYP450 inhibitors for 3A4, 2C8, 2C9, 1A2 or 2D6 isoenzymes, respectively. The substrate, inhibitor plus Idarubicin as indicated are added to each protein sample are incubated for 20 minutes- 60 minutes, as recommend by manufacturer, at 37C. Reactions are stopped with an organic solvent solution and then samples are analyzed by fluorescence plate reader as appropriate. For each experiment, control samples with a known amount of substrate and synthesized metabolite, in the absence of the isoenzyme, are prepared for qualitative comparisons. All experiments are performed in triplicate.

533, 95

DMSO 107 mg/mL, Water 10 mg/mL, Ethanol <1 mg/mL