| 名稱 | Idarubicin hydrochloride |
| 描述 | Idarubicin hydrochloride (Zavedos), a hydrochloride salt form of Idarubicin, is a DNA topoisomerase II (topo II) inhibitor for MCF-7 cells ( IC50: 3.3 ng/mL). |
| 細(xì)胞實(shí)驗(yàn) | The anti-proliferative activity of the Idarubicin in the conjugate is compared to that of free drug by measuring the inhibition of [3H]thymidine uptake. Briefly, NALM-6 cells (1.5 × 106/mL) are added to a flat-bottomed microtitre plate (100 μL/well) and incubated for 1 hours at 37ºC. Free Idarubicin and Idarubicin-mAb conjugates are sterilised by filtration and diluted in sterile PBS; various concentrations are added to the wells (100 μL/well) in duplicate and the plates are incubated at 37ºC, 7% CO2 for 24 hours. Following incubation, 50 μL medium containing 1 μCi [3H]thymidine is added to each well and the plates are incubated for a further 4 hours. Cells are harvested onto glass-fibre filter-paper, dried and counted in a scintillation counter. Specificity studies are performed using the same technique where the ability of Idarubicin-anti-CD19 conjugates to kill CD19 + cells is compared to the cytotoxicity of irrelevant Idarubicin-JGT conjugates. NALM-6 cells (1.5× 106/mL, 300 μL tube) are incubated for 30 rain on ice with various concentrations of Idarubicin-anti-CD 19 or Idarubicin-JGT conjugates. Following three washes in ice-cold RPMI-1640 medium (4 mL/wash), the cells are resuspended in fresh medium and transferred to 96-well plates (100 μL/well). Each tube is set up in duplicate and two wells are plated out per tube (a total of 4 wells per drug concentration). Cells are pulsed with [3H]thymidine 24 hours later and harvested. (Only for Reference) |
| 激酶實(shí)驗(yàn) | 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 37oC. 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. |
| 體外活性 | Idarubicin對(duì)多細(xì)胞球體展現(xiàn)出顯著的細(xì)胞毒性活性，與其對(duì)單層細(xì)胞的抗增殖效果相當(dāng)。[1] Idarubicin還能抑制CYP450 2D6的活性。[2] 與多柔比星和表柔比星相比，Idarubicin的活性分別約為57.5倍和25倍。Idarubicin能夠克服P-糖蛋白介導(dǎo)的多藥耐藥性。[3] Idarubicin能夠抑制中性粒細(xì)胞超氧化物自由基的形成。[4] Idarubicin可以與單克隆抗體（抗Ly-2.1、抗L3T4或抗Thy-1）耦合，同時(shí)保持蛋白質(zhì)的溶解性和抗體活性。[5] Idarubicin抑制NALM-6細(xì)胞的增殖，IC50為12 nM。[6] |
| 體內(nèi)活性 | Idarubicin的還原依賴于酮還原酶，并且相較于大多數(shù)酮類化合物，其還原過程具有更高的立體選擇性，幾乎專一性地生成(13S)-表構(gòu)異構(gòu)體。Idarubicin還原的高立體特異性可能源自于其羰基附近不對(duì)稱中心的手性誘導(dǎo)效應(yīng)。[7] |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : 5 mg/mL (9.36 mM)
DMSO : 93 mg/mL (174.2 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | Autophagy | DNA synthesis | DNA/RNA Synthesis | MCF-7 | Myc | Bacterial | breast tumor | leukaemias | Idarubicin Hydrochloride | c-Myc | Inhibitor | Idarubicin | Topoisomerase | Fungal | inhibit | Antibiotic | 4-Demethoxydaunorubicin | Idarubicin hydrochloride | 4-Demethoxydaunorubicin Hydrochloride |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Doxycycline | Neomycin sulfate | Hydroxychloroquine | Dimethyl sulfoxide | Stavudine | Ampicillin sodium | Sulfamethoxazole sodium | Paeonol | Kanamycin sulfate | Sodium 4-phenylbutyrate |
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