| 名稱 | Ifosfamide |
| 描述 | Ifosfamide (NSC-109724) alkylates and forms DNA crosslinks, thereby preventing DNA strand separation and DNA replication. Ifosfamide is a synthetic analog of the nitrogen mustard cyclophosphamide with antineoplastic activity. This agent is a prodrug that must be activated through hydroxylation by hepatic microsomal enzymes. |
| 激酶實(shí)驗(yàn) | cAMP kinase assay: Diced epididymal fat pads from fed Wistar rats (175-225 gm) are obtained after decapitation and incubated at 37 °C for two hours in Krebs-bicarbonate buffer containing 1.27 mM CaCl2. When added, Tolbutamide is present only during the incubation. After incubation fat pads are rinsed and sonicated in cold Krebs-bicarbonate buffer. The aqueous supematants from centrifugation at 50,000 × g for 30 minutes at 4 °C contained 0.75 to 1.25 mg protein per mL and are assayed for cyclic AMP-stimulated protein kinase activity. The assay is performed in 0.2 mL with these additions, 10 μmoles sodium glycerofiosphate pH 7.0, 2 μmoles sodium fluoride, 0.4 μmoles theophylline, 0.1 μmoles ethylene glyool bis (β-aminoethyl ether)-N, N'-tetraaoetic acid, 3 μmoles magnesium chloride, 0.3 mg mixed histone, 2 nmoles (γ- 32P) ATP, 1 nmoles cyclic AMP when indicated, and 0.05 ml of supernatant. |
| 體外活性 | Ifosfamide誘導(dǎo)膀胱水腫,在Ifosfamide注射液后12小時(shí)達(dá)到峰值.顯微分析顯示血管充血、水腫、出血、纖維蛋白沉積、中性粒細(xì)胞浸潤和上皮剝蝕.誘導(dǎo)型一氧化氮合酶免疫反應(yīng)在膀胱上皮細(xì)胞的細(xì)胞質(zhì)中表現(xiàn)出強(qiáng)烈的反應(yīng)性,可見彌漫性壞死.腹膜內(nèi)注射給小鼠100 mg/kg,200 mg/kg和400 mg/kg Ifosfamide,依賴于劑量地誘導(dǎo)膀胱濕重和Evans藍(lán)外滲的增加.用mesna預(yù)處理可減少膀胱水腫的增加,而l - ng -硝基精氨酸甲酯、抗血清TNF-alpha或IL-1beta、thalidomide或pentoxifylline的治療可抑制膀胱水腫和顯微改變.抗血清治療也抑制了誘導(dǎo)型一氧化氮合酶在尿道上皮內(nèi)的表達(dá).誘導(dǎo)型一氧化氮合酶產(chǎn)生的一氧化氮參與了尿路上皮細(xì)胞的損傷,并參與了在小鼠的ifosfamide管理后導(dǎo)致出血性膀胱炎的炎癥反應(yīng). |
| 體內(nèi)活性 | 在肝臟中,Ifosfamide它是一種由細(xì)胞色素P450混合功能氧化酶轉(zhuǎn)化為活性烷基化化合物的原藥物。在小兒實(shí)體瘤,卵巢癌,小細(xì)胞肺癌,非霍奇金和霍奇金淋巴瘤中,Ifosfamide均有良好的抗腫瘤效果。Ifosfamide（50 mM）使肝細(xì)胞中的CYP2C8/9,CYP3A4蛋白水平上升,進(jìn)而使肝細(xì)胞自身的4-羥基化率提升。在CYP3A4表達(dá)量高于CYP3A5的肝細(xì)胞中,Ifosfamide僅誘導(dǎo)CYP3A4的表達(dá)。Ifosfamide對(duì)穩(wěn)定轉(zhuǎn)染CYP2B1的MCF-7細(xì)胞有較強(qiáng)細(xì)胞毒性（可被CYP2B1抑制劑美替拉酮顯著降低）,但不影響β-半乳糖苷酶表達(dá)和親本腫瘤細(xì)胞的MCF-7細(xì)胞。在預(yù)防腫瘤復(fù)發(fā)時(shí),Ifosfamide和唑來膦酸聯(lián)用比單獨(dú)用藥,對(duì)骨形成的增加,組織修復(fù)的提高更有效。 |
| 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 : 48 mg/mL (183.8 mM)
DMSO : 55 mg/mL (210.66 mM)
Ethanol : 49 mg/mL (187.7 mM)
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| 關(guān)鍵字 | inhibit | DNA Alkylator/Crosslinker | NSC-109724 | Ifosfamide | Inhibitor | NSC 109724 |
| 相關(guān)產(chǎn)品 | N-Nitrosodiethylamine | Acyclovir | 2,4-D | Guanidine hydrochloride | Procaine | Folic acid | 5-Fluorouracil | Temozolomide | Thymidine | Ribavirin | Azelaic acid | Rifampicin |
| 相關(guān)庫 | 抗癌活性化合物庫 | 抗癌上市藥物庫 | 經(jīng)典已知活性庫 | FDA 上市藥物庫 | 藥物功能重定位化合物庫 | 酪氨酸激酶分子庫 | 抗癌臨床化合物庫 |